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Lorlatinib: Drug information

Lorlatinib: Drug information
2025© UpToDate, Inc. and its affiliates and/or licensors. All Rights Reserved.
For additional information see "Lorlatinib: Patient drug information"

For abbreviations, symbols, and age group definitions show table
Brand Names: US
  • Lorbrena
Brand Names: Canada
  • Lorbrena
Pharmacologic Category
  • Antineoplastic Agent, Anaplastic Lymphoma Kinase Inhibitor;
  • Antineoplastic Agent, Tyrosine Kinase Inhibitor
Dosing: Adult

Dosage guidance:

Safety: Control BP prior to lorlatinib initiation.

Non–small cell lung cancer, metastatic, ALK positive

Non–small cell lung cancer, metastatic, ALK positive:

Note: Select patients for the treatment based on ALK positivity in tumor specimens.

Oral: 100 mg once daily; continue until disease progression or unacceptable toxicity (Ref).

Non–small cell lung cancer, metastatic, ROS1 positive

Non–small cell lung cancer, metastatic, ROS1 positive (off-label use): Oral: 100 mg once daily; continue until disease progression or unacceptable toxicity (Ref).

Missed doses: If a dose is missed, administer the missed dose unless the next dose is due within 4 hours. Do not administer 2 doses at the same time to make up for a missed dose. If vomiting occurs, do not administer an additional dose; continue with the next scheduled dose.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Note: Kidney function estimated using the Cockcroft-Gault formula.

CrCl 30 to 89 mL/minute: No dosage adjustment necessary.

CrCl 15 to <30 mL/minute: Reduce dose to 75 mg once daily.

End-stage kidney impairment requiring dialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Liver Impairment: Adult

Mild impairment (total bilirubin ≤ ULN with AST > ULN or total bilirubin >1 to 1.5 times ULN with any AST): No dosage adjustment necessary.

Moderate impairment (total bilirubin ≥1.5 to 3 times ULN with any AST) or severe impairment (total bilirubin >3 times ULN with any AST): There are no dosage adjustments provided in the manufacturer's labeling (has not been established).

Dosing: Adjustment for Toxicity: Adult
Lorlatinib Dose Reduction Levels for Adverse Reactions

Dosage reduction levels

Recommended lorlatinib dosage and schedule

Initial (usual) dose

100 mg once daily

First dose reduction

75 mg once daily

Second dose reduction

50 mg once daily

Subsequent

Permanently discontinue lorlatinib if unable to tolerate 50 mg once daily.

Lorlatinib Recommended Dose Modifications for Adverse Reactions

Adverse reaction

Severity

Lorlatinib dose modification

a ILD = interstitial lung disease.

Cardiovascular toxicity

Atrioventricular (AV) block

Second-degree AV block

Withhold lorlatinib until PR interval is <200 msec, and then resume lorlatinib at a reduced dose.

Complete AV block (first occurrence)

Withhold lorlatinib until either pacemaker is placed or PR interval is <200 msec. If a pacemaker is placed, resume lorlatinib at the same dose. If no pacemaker is placed, resume lorlatinib at a reduced dose.

Complete AV block (recurrent)

Place pacemaker or permanently discontinue lorlatinib.

Hypertension

Grade 3 (systolic BP [SBP] ≥160 mm Hg or diastolic BP [DBP] ≥100 mm Hg; medical intervention indicated; >1 antihypertensive medication, or more intensive therapy than previously used indicated)

Withhold lorlatinib until hypertension has recovered to ≤ grade 1 (SBP <140 mm Hg and DBP <90 mm Hg), then resume lorlatinib at the same dose. If grade 3 hypertension recurs, withhold lorlatinib until recovery to ≤ grade 1, then resume at a reduced dose. If hypertension cannot be adequately controlled with optimal medical management, permanently discontinue lorlatinib.

Grade 4 (life-threatening consequences, urgent intervention indicated)

Withhold lorlatinib until recovery to ≤ grade 1, then resume at a reduced dose or permanently discontinue lorlatinib.

Recurrent grade 4 hypertension

Permanently discontinue lorlatinib.

CNS toxicity

CNS effects (eg, seizures, psychotic effects, changes in cognitive function, mood [including suicidal ideation], speech, mental status, sleep)

Grade 1

Continue lorlatinib at the same dose or withhold until recovery to baseline. Resume lorlatinib at the same dose or at a reduced dose.

Grade 2 or 3

Withhold dose until resolved to grade 0 or 1, then resume lorlatinib at a reduced dose.

Grade 4

Permanently discontinue lorlatinib.

Metabolic toxicity

Hyperglycemia

Grade 3 (fasting serum glucose >250 mg/dL despite optimal antihyperglycemic therapy) or grade 4

Withhold lorlatinib until hyperglycemia is appropriately controlled, then resume at the next lower dose. If hyperglycemia cannot be adequately controlled with optimal medical management, permanently discontinue lorlatinib.

Hyperlipidemia

Grade 4 hypercholesterolemia or grade 4 hypertriglyceridemia

Withhold lorlatinib until recovery of hypercholesterolemia and/or hypertriglyceridemia to ≤ grade 2 and then resume lorlatinib at the same dose. If severe hypercholesterolemia and/or hypertriglyceridemia recurs, resume lorlatinib at a reduced dose. Hyperlipidemia may require initiation (or increased doses) of lipid-lowering agents.

Pulmonary toxicity

Treatment-related ILDa/pneumonitis

Any grade

Immediately withhold lorlatinib and promptly evaluate if ILD/pneumonitis is suspected. Permanently discontinue lorlatinib for ILD/pneumonitis of any severity.

Other adverse reactions

Grade 1 or 2

Continue lorlatinib at the same dose or at a reduced dose.

Grade 3 or 4

Withhold lorlatinib until symptoms resolve to ≤ grade 2 or baseline, then resume lorlatinib at a reduced dose.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Cardiovascular: Chest pain (11%), edema (56% to 57%), hypertension (18%)

Dermatologic: Skin rash (11% to 14%)

Endocrine & metabolic: Hypercholesterolemia (91% to 96%), hyperglycemia (48% to 52%), hyperkalemia (21%), hypertriglyceridemia (90% to 95%), hypoalbuminemia (33% to 36%), hypomagnesemia (21%), hypophosphatemia (21%), increased amylase (20% to 22%), increased gamma-glutamyl transferase (52%), weight gain (24% to 38%)

Gastrointestinal: Constipation (15% to 17%), diarrhea (21% to 22%), increased serum lipase (24% to 28%), nausea (15% to 18%), vomiting (12% to 13%)

Hematologic & oncologic: Anemia (48% to 52%; grade 3/4: 2% to 5%), lymphocytopenia (22% to 23%; grades 3/4: 3%), prolonged prothrombin time (25%), thrombocytopenia (23%; grade 3/4: <1%)

Hepatic: Increased serum alanine aminotransferase (28% to 44%), increased serum alkaline phosphatase (23% to 24%), increased serum aspartate aminotransferase (37% to 48%)

Nervous system: Cognitive dysfunction (21% to 27%), dizziness (11% to 16%), fatigue (19% to 26%), headache (17% to 18%), mood disorder (16% to 23%), peripheral neuropathy (34% to 47%; grade 3/4: 2% to 3%), sleep disorder (10% to 11%), speech disturbance (7% to 12%)

Neuromuscular & skeletal: Arthralgia (19% to 23%), back pain (13% to 15%), increased creatine phosphokinase in blood specimen (39%), limb pain (13% to 17%), myalgia (15% to 17%)

Ophthalmic: Visual disturbance (15% to 18%)

Renal: Increased serum creatinine (81%)

Respiratory: Cough (16% to 18%), dyspnea (20% to 27%), upper respiratory tract infection (11% to 12%)

Miscellaneous: Fever (12% to 17%)

1% to 10%:

Nervous system: Mental status changes (1%), psychotic reaction (3% to 7%)

Respiratory: Bronchitis (7%), pneumonia (3% to 7%), respiratory failure (1% to 3%)

Frequency not defined:

Cardiovascular: Atrioventricular block

Nervous system: Seizure

Respiratory: Interstitial pulmonary disease, pneumonitis

Contraindications

Concomitant use of strong CYP3A inducers.

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Canadian labeling: Additional contraindications (not in the US labeling): Hypersensitivity to lorlatinib or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• Cardiovascular effects: PR interval prolongation and atrioventricular block may rarely occur in patients receiving lorlatinib, including grade 3 events. Some patients required pacemaker placement.

• CNS effects: CNS effects (including seizures, psychotic effects/changes and cognitive function, mood [including suicidal ideation], speech, mental status, and sleep changes) may occur in patients receiving lorlatinib. Overall, CNS effects occurred in just over half of patients receiving lorlatinib. Cognitive effects occurred in nearly one-third patients who received lorlatinib (at any dose) in one study; a small percentage of these events were severe (grade 3 or 4). Mood effects occurred in nearly one-fourth of patients; severe events occurred rarely. Speech effects, hallucinations, and mental status changes have also been reported, including rare severe events. Seizures have been observed, sometimes in conjunction with other neurologic findings. Changes in sleep have also been reported. The median time to initial onset of any CNS effect was 1.4 months (range: 1 day to 3.4 years).

• Hyperglycemia: Hyperglycemia has been reported, including grade 3 or 4 events. The median time to onset of hyperglycemia was 4.8 months (range: 1 day to 2.9 years).

• Hyperlipidemia: Serum cholesterol and triglycerides increases may occur in patients receiving lorlatinib. Grade 3 or 4 total cholesterol and triglyceride elevations have been reported. The median time to onset (for both hypercholesterolemia and hypertriglyceridemia) was 15 days. A majority of patients with hypercholesterolemia and hypertriglyceridemia required initiation of lipid-lowering medications, usually at ~17 days after lorlatinib initiation.

• Hypertension: Hypertension may occur, including grade 3 and 4 events. The median time to onset of hypertension was 6.4 months (range: 1 day to 2.8 years).

• Pulmonary toxicity: Severe or life-threatening pulmonary adverse reactions consistent with interstitial lung disease (ILD)/pneumonitis may rarely occur with lorlatinib, including grades 3 and 4 events. Symptoms indicative of ILD/pneumonitis include dyspnea, cough, and fever.

Other warnings/precautions:

• ALK positivity: Select patients for the treatment of metastatic non-small cell lung cancer based on the presence of ALK positivity in tumor specimens. Information on approved tests for detection of ALK gene rearrangements may be found at https://www.fda.gov/CompanionDiagnostics.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Lorbrena: 25 mg, 100 mg

Generic Equivalent Available: US

No

Pricing: US

Tablets (Lorbrena Oral)

25 mg (per each): $284.79

100 mg (per each): $854.38

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Lorbrena: 25 mg, 100 mg

Administration: Adult

Oral: Administer at the same time each day, with or without food. Swallow intact tablets whole; do not chew, crush, or split; do not ingest tablets that are broken, cracked, or otherwise not intact.

Hazardous Drugs Handling Considerations

This medication is not on the NIOSH (2024) list; however, it may meet the criteria for a hazardous drug. Lorlatinib may cause teratogenicity and has a structural/toxicity profile similar to existing hazardous agents.

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).

Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.

Use: Labeled Indications

Non–small cell lung cancer, metastatic, ALK positive: Treatment of metastatic non–small cell lung cancer in adults whose tumors are ALK positive (as detected by an approved test).

Use: Off-Label: Adult

Non–small cell lung cancer, metastatic, ROS1 positive

Medication Safety Issues
Sound-alike/look-alike issues:

Lorlatinib may be confused with alectinib, brigatinib, ceritinib, crizotinib, erlotinib, lapatinib, larotrectinib, lenvatinib, loratadine, lorazepam, lornafarnib.

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).

Metabolism/Transport Effects

Substrate of CYP3A4 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces CYP2B6 (Weak), CYP3A4 (Moderate), P-glycoprotein;

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Abemaciclib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Abemaciclib. Risk X: Avoid

Abiraterone Acetate: CYP3A4 Inducers (Moderate) may decrease serum concentration of Abiraterone Acetate. Risk C: Monitor

Acalabrutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Acalabrutinib. Risk C: Monitor

Acetaminophen: Lorlatinib may decrease serum concentration of Acetaminophen. Risk C: Monitor

Afatinib: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Afatinib. Management: Increase the afatinib dose by 10 mg as tolerated in patients requiring chronic coadministration of P-gp inducers with afatinib. Reduce afatinib dose back to the original afatinib dose 2 to 3 days after discontinuation of the P-gp inducer. Risk D: Consider Therapy Modification

ALfentanil: CYP3A4 Inducers (Moderate) may decrease serum concentration of ALfentanil. Management: If concomitant use of alfentanil and moderate CYP3A4 inducers is necessary, consider dosage increase of alfentanil until stable drug effects are achieved. Monitor patients for signs of opioid withdrawal. Risk D: Consider Therapy Modification

Aliskiren: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Aliskiren. Risk C: Monitor

Alpelisib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Alpelisib. Risk C: Monitor

ALPRAZolam: CYP3A4 Inducers (Moderate) may decrease serum concentration of ALPRAZolam. Risk C: Monitor

AmLODIPine: CYP3A4 Inducers (Moderate) may decrease serum concentration of AmLODIPine. Risk C: Monitor

Androgens: Hypertension-Associated Agents may increase hypertensive effects of Androgens. Risk C: Monitor

Antidiabetic Agents: Hyperglycemia-Associated Agents may decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor

Antihepaciviral Combination Products: CYP3A4 Inducers (Moderate) may decrease serum concentration of Antihepaciviral Combination Products. Risk X: Avoid

Apixaban: Inducers of CYP3A4 (Moderate) and P-glycoprotein may decrease serum concentration of Apixaban. Risk C: Monitor

Apremilast: CYP3A4 Inducers (Moderate) may decrease serum concentration of Apremilast. Risk C: Monitor

Aprepitant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Aprepitant. Risk C: Monitor

ARIPiprazole Lauroxil: CYP3A4 Inducers (Moderate) may decrease serum concentration of ARIPiprazole Lauroxil. Risk C: Monitor

ARIPiprazole: CYP3A4 Inducers (Moderate) may decrease serum concentration of ARIPiprazole. Risk C: Monitor

Artemether and Lumefantrine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Artemether and Lumefantrine. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be decreased. Risk C: Monitor

Atogepant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Atogepant. Management: For treatment of episodic migraine, the recommended dose of atogepant is 30 mg once daily or 60 mg once daily when combined with CYP3A4 inducers. When used for treatment of chronic migraine, use of atogepant with CYP3A4 inducers should be avoided. Risk D: Consider Therapy Modification

Atorvastatin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Atorvastatin. Risk C: Monitor

Atrasentan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Atrasentan. Risk X: Avoid

Avacopan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Avacopan. Risk X: Avoid

Avanafil: CYP3A4 Inducers (Moderate) may decrease serum concentration of Avanafil. Risk X: Avoid

Avapritinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Avapritinib. Risk X: Avoid

Axitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Axitinib. Management: Concurrent use of axitinib with a moderate CYP3A4 inducer should be avoided when possible. If any such combination is necessary, monitor for reduced axitinib efficacy. Risk D: Consider Therapy Modification

Bedaquiline: CYP3A4 Inducers (Moderate) may decrease serum concentration of Bedaquiline. CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Bedaquiline. Risk X: Avoid

Belumosudil: CYP3A4 Inducers (Moderate) may decrease serum concentration of Belumosudil. Risk C: Monitor

Benzhydrocodone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Benzhydrocodone. Specifically, the serum concentrations of hydrocodone may be reduced. Risk C: Monitor

Berotralstat: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Berotralstat. Risk X: Avoid

Beta-Acetyldigoxin: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Beta-Acetyldigoxin. Risk C: Monitor

Bortezomib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Bortezomib. Risk C: Monitor

Bosutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Bosutinib. Risk C: Monitor

Brexpiprazole: CYP3A4 Inducers (Moderate) may decrease serum concentration of Brexpiprazole. Risk C: Monitor

Brigatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inducers when possible. If combined, increase the daily dose of brigatinib in 30 mg increments after 7 days of treatment with the current brigatinib dose, up to maximum of twice the dose. Risk D: Consider Therapy Modification

Buprenorphine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Buprenorphine. Risk C: Monitor

BuPROPion: CYP2B6 Inducers (Weak) may decrease serum concentration of BuPROPion. Risk C: Monitor

BusPIRone: CYP3A4 Inducers (Moderate) may decrease serum concentration of BusPIRone. Risk C: Monitor

Cabozantinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Cabozantinib. Management: For cabozantinib tablets (Cabometyx), avoid combined use if possible. If combined, increase cabozantinib by 20 mg from previous dose, max 80 mg daily. For cabozantinib capsules (Cometriq), monitor for reduced cabozantinib efficacy if combined. Risk D: Consider Therapy Modification

Calcifediol: CYP3A4 Inducers (Moderate) may decrease serum concentration of Calcifediol. Risk C: Monitor

Calcitriol (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Calcitriol (Systemic). Risk C: Monitor

Cannabis: CYP3A4 Inducers (Moderate) may decrease serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. Risk C: Monitor

Capivasertib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Capivasertib. Risk X: Avoid

Capmatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Capmatinib. Risk X: Avoid

Cariprazine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Cariprazine. Risk X: Avoid

Celiprolol: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Celiprolol. Risk C: Monitor

Cladribine: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Cladribine. Risk C: Monitor

Clarithromycin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Clarithromycin. CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Clarithromycin. Management: Consider alternative antimicrobial therapy for patients receiving a CYP3A4 inducer. Drugs that enhance the metabolism of clarithromycin into 14-hydroxyclarithromycin may alter the clinical activity of clarithromycin and impair its efficacy. Risk D: Consider Therapy Modification

Clindamycin (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Clindamycin (Systemic). Risk C: Monitor

Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor

CloZAPine: CYP3A4 Inducers (Moderate) may decrease serum concentration of CloZAPine. Risk C: Monitor

Cobimetinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Cobimetinib. Risk X: Avoid

Codeine: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Codeine. Risk C: Monitor

Copanlisib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Copanlisib. Risk C: Monitor

Crinecerfont: CYP3A4 Inducers (Moderate) may decrease serum concentration of Crinecerfont. Management: Double the evening dose of crinecerfont and continue the morning dose unchanged during coadministration with moderate CYP3A4 inducers. See full interaction monograph for details. Risk D: Consider Therapy Modification

Crizotinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Crizotinib. Risk C: Monitor

CycloSPORINE (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of CycloSPORINE (Systemic). Risk C: Monitor

CYP3A4 Inducers (Moderate): May increase hepatotoxic effects of Lorlatinib. CYP3A4 Inducers (Moderate) may decrease serum concentration of Lorlatinib. Management: Avoid use of lorlatinib with moderate CYP3A4 inducers. If such a combination must be used, increase lorlatinib to 125 mg daily. Monitor for reduced lorlatinib efficacy and consider closer monitoring of AST, ALT, and bilirubin. Risk D: Consider Therapy Modification

CYP3A4 Inducers (Strong): May increase hepatotoxic effects of Lorlatinib. CYP3A4 Inducers (Strong) may decrease serum concentration of Lorlatinib. Risk X: Avoid

CYP3A4 Inhibitors (Strong): May increase serum concentration of Lorlatinib. Management: Avoid use of lorlatinib with strong CYP3A4 inhibitors. If the combination cannot be avoided, reduce the lorlatinib dose from 100 mg once daily to 75 mg once daily, or from 75 mg once daily to 50 mg once daily. Risk D: Consider Therapy Modification

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Dabigatran Etexilate. Management: Avoid concurrent use of dabigatran with P-glycoprotein inducers whenever possible. Risk X: Avoid

Daclatasvir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Daclatasvir. Management: Increase the daclatasvir dose to 90 mg once daily if used with a moderate CYP3A4 inducer. Risk D: Consider Therapy Modification

Dapsone (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Dapsone (Systemic). Risk C: Monitor

Daridorexant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Daridorexant. Risk X: Avoid

Darolutamide: Inducers of CYP3A4 (Moderate) and P-glycoprotein may decrease serum concentration of Darolutamide. Risk X: Avoid

Dasabuvir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Dasabuvir. Risk X: Avoid

Dasatinib: CYP3A4 Inducers (Moderate) may increase serum concentration of Dasatinib. Risk C: Monitor

Deflazacort: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Deflazacort. Risk X: Avoid

DexAMETHasone (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of DexAMETHasone (Systemic). Risk C: Monitor

DiazePAM: CYP3A4 Inducers (Moderate) may decrease serum concentration of DiazePAM. Risk C: Monitor

Dienogest: CYP3A4 Inducers (Moderate) may decrease serum concentration of Dienogest. Risk C: Monitor

Digitoxin: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Digitoxin. Risk C: Monitor

Digoxin: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Digoxin. Risk C: Monitor

DilTIAZem: CYP3A4 Inducers (Moderate) may decrease serum concentration of DilTIAZem. Risk C: Monitor

Disopyramide: CYP3A4 Inducers (Moderate) may decrease serum concentration of Disopyramide. Risk C: Monitor

Doravirine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Doravirine. Risk C: Monitor

DOXOrubicin (Conventional): CYP3A4 Inducers (Moderate) may decrease serum concentration of DOXOrubicin (Conventional). Risk X: Avoid

DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inducers may decrease serum concentration of DOXOrubicin (Conventional). Risk X: Avoid

DroNABinol: CYP3A4 Inducers (Moderate) may decrease serum concentration of DroNABinol. Risk C: Monitor

Dronedarone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Dronedarone. Risk C: Monitor

Duvelisib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Duvelisib. Management: Avoid if possible. If used, on day 12 of combination increase duvelisib from 25 mg twice daily to 40 mg twice daily or from 15 mg twice daily to 25 mg twice daily. Resume prior duvelisib dose 14 days after stopping moderate CYP3A4 inducer. Risk D: Consider Therapy Modification

Dydrogesterone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Dydrogesterone. Risk C: Monitor

Edoxaban: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Edoxaban. Management: Avoid coadministration of edoxaban and P-glycoprotein (P-gp) inducers if possible. If concomitant use is required, be aware the edoxaban efficacy may be decreased. Risk D: Consider Therapy Modification

Elacestrant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Elacestrant. Risk X: Avoid

Elbasvir and Grazoprevir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid

Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Risk C: Monitor

Eliglustat: CYP3A4 Inducers (Moderate) may decrease serum concentration of Eliglustat. Risk C: Monitor

Ensartinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ensartinib. Risk X: Avoid

Entrectinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Entrectinib. Risk X: Avoid

Erdafitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Erdafitinib. Management: If a moderate CYP3A4 inducer must be used at the start of erdafitinib, administer erdafitinib at a dose of 9 mg daily. If a moderate CYP3A4 inducer is discontinued, continue erdafitinib at the same dose unless there is evidence of drug toxicity. Risk D: Consider Therapy Modification

Erlotinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Erlotinib. Management: Avoid the combination of erlotinib and strong CYP3A4 inducers whenever possible. If this combination must be used, increase erlotinib dose by 50 mg increments every 2 weeks as tolerated, to a maximum of 450 mg/day. Risk D: Consider Therapy Modification

Estrogen Derivatives: CYP3A4 Inducers (Moderate) may decrease serum concentration of Estrogen Derivatives. Risk C: Monitor

Etoposide Phosphate: CYP3A4 Inducers (Moderate) may decrease serum concentration of Etoposide Phosphate. Risk C: Monitor

Etoposide: CYP3A4 Inducers (Moderate) may decrease serum concentration of Etoposide. Risk C: Monitor

Everolimus: CYP3A4 Inducers (Moderate) may decrease serum concentration of Everolimus. Risk C: Monitor

Exemestane: CYP3A4 Inducers (Moderate) may decrease serum concentration of Exemestane. Risk C: Monitor

Fedratinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Fedratinib. Risk X: Avoid

Felodipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Felodipine. Risk C: Monitor

FentaNYL: CYP3A4 Inducers (Moderate) may decrease serum concentration of FentaNYL. Risk C: Monitor

Fexinidazole: CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Fexinidazole. Risk X: Avoid

Fexofenadine: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Fexofenadine. Risk C: Monitor

Finerenone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Finerenone. Risk X: Avoid

Flibanserin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Flibanserin. Risk X: Avoid

Fluconazole: May increase serum concentration of Lorlatinib. Management: Avoid use of lorlatinib with fluconazole whenever possible. If the combination cannot be avoided, reduce the lorlatinib dose from 100 mg once daily to 75 mg once daily. Risk D: Consider Therapy Modification

Fosamprenavir: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Fosamprenavir. Risk C: Monitor

Fosaprepitant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite aprepitant. Risk C: Monitor

Fosnetupitant: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Fosnetupitant. Risk C: Monitor

Fostamatinib: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Fostamatinib. Risk C: Monitor

Fruquintinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Fruquintinib. Management: Avoid this combination when possible. If combined, continue the same fruquintinib dose, but monitor for reduced fruquintinib efficacy. Risk D: Consider Therapy Modification

Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification

Futibatinib: Inducers of CYP3A4 (Moderate) and P-glycoprotein may decrease serum concentration of Futibatinib. Risk C: Monitor

Ganaxolone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ganaxolone. Management: Avoid concomitant use of ganaxolone and moderate CYP3A4 inducers whenever possible. If combined, consider increasing the dose of ganaxolone, but do not exceed the maximum recommended daily dose. Risk D: Consider Therapy Modification

Gefitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Gefitinib. Risk C: Monitor

Gemigliptin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Gemigliptin. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Gemigliptin. Risk C: Monitor

Gepirone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Gepirone. Risk C: Monitor

Gepotidacin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Gepotidacin. Risk C: Monitor

Gilteritinib: Inducers of CYP3A4 (Moderate) and P-glycoprotein may decrease serum concentration of Gilteritinib. Risk C: Monitor

Glasdegib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Glasdegib. Management: Avoid use of glasdegib and moderate CYP3A4 inducers whenever possible. If combined, increase glasdegib dose from 100 mg daily to 200 mg daily or from 50 mg daily to 100 mg daily. Resume previous glasdegib dose 7 days after discontinuation of the inducer. Risk D: Consider Therapy Modification

Glecaprevir and Pibrentasvir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor

GuanFACINE: CYP3A4 Inducers (Moderate) may decrease serum concentration of GuanFACINE. Management: Increase extended-release guanfacine dose by up to double when initiating guanfacine in patients taking CYP3A4 inducers or if initiating a CYP3A4 inducer in a patient already taking extended-release guanfacine. Monitor for reduced guanfacine efficacy. Risk D: Consider Therapy Modification

Hormonal Contraceptives: CYP3A4 Inducers (Moderate) may decrease serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a moderate CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider Therapy Modification

HYDROcodone: CYP3A4 Inducers (Moderate) may decrease serum concentration of HYDROcodone. Risk C: Monitor

Hydrocortisone (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Hydrocortisone (Systemic). Risk C: Monitor

Ibrexafungerp: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ibrexafungerp. Risk X: Avoid

Ibrutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ibrutinib. Risk C: Monitor

Ifosfamide: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Ifosfamide. CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Ifosfamide. Risk C: Monitor

Imatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Imatinib. Risk C: Monitor

Indinavir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Indinavir. Management: Consider avoiding the combination of indinavir and moderate CYP3A4 inducers whenever possible due to the risk for decreased indinavir concentrations, reduced efficacy, and development of resistance. If combined, monitor for indinavir treatment failure. Risk D: Consider Therapy Modification

Irinotecan Products: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Irinotecan Products. Specifically, concentrations of SN-38 may be reduced. Risk C: Monitor

Isavuconazonium Sulfate: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Isavuconazonium Sulfate. Specifically, CYP3A4 Inducers (Moderate) may decrease isavuconazole serum concentrations. Risk C: Monitor

Isradipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Isradipine. Risk C: Monitor

Istradefylline: CYP3A4 Inducers (Moderate) may decrease serum concentration of Istradefylline. Risk C: Monitor

Ivabradine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ivabradine. Risk X: Avoid

Ivacaftor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ivacaftor. Risk C: Monitor

Ixabepilone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ixabepilone. Risk C: Monitor

Ixazomib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ixazomib. Risk C: Monitor

Ketamine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ketamine. Risk C: Monitor

Lapatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lapatinib. Risk C: Monitor

Larotrectinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Larotrectinib. Management: Double the larotrectinib dose if used together with a moderate CYP3A4 inducer. Following discontinuation of the moderate CYP3A4 inducer, resume the previous dose of larotrectinib after a period of 3 to 5 times the inducer's half-life. Risk D: Consider Therapy Modification

Lazertinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lazertinib. Risk X: Avoid

Ledipasvir: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Ledipasvir. Risk X: Avoid

Lefamulin (Intravenous): CYP3A4 Inducers (Moderate) may decrease serum concentration of Lefamulin (Intravenous). Management: Avoid concomitant use of lefamulin (intravenous) with moderate CYP3A4 inducers unless the benefits outweigh the risks. Risk D: Consider Therapy Modification

Lefamulin (Intravenous): P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Lefamulin (Intravenous). Management: Avoid concomitant use of lefamulin (intravenous) with P-glycoprotein/ABCB1 inducers unless the benefits outweigh the risks. Risk D: Consider Therapy Modification

Lefamulin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin with moderate CYP3A4 inducers unless the benefits outweigh the risks. Risk D: Consider Therapy Modification

Lefamulin: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin with P-glycoprotein/ABCB1 inducers unless the benefits outweigh the risks. Risk D: Consider Therapy Modification

Lemborexant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lemborexant. Risk X: Avoid

Lenacapavir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lenacapavir. Risk X: Avoid

Leniolisib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Leniolisib. Risk X: Avoid

Lercanidipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lercanidipine. Risk C: Monitor

Letermovir: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Letermovir. Risk X: Avoid

Levamlodipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Levamlodipine. Risk C: Monitor

Levomethadone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Levomethadone. Risk C: Monitor

LinaGLIPtin: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of LinaGLIPtin. Management: Strongly consider using an alternative to any P-glycoprotein inducer in patients who are being treated with linagliptin. If this combination is used, monitor patients closely for evidence of reduced linagliptin effectiveness. Risk D: Consider Therapy Modification

Lonafarnib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lonafarnib. Risk X: Avoid

Lovastatin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lovastatin. Risk C: Monitor

Lumateperone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lumateperone. Risk X: Avoid

Lurasidone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lurasidone. Management: After chronic treatment (7 days or more) with a moderate CYP3A4 inducer, lurasidone dose increases may be needed. Monitor closely for decreased lurasidone effects and increase the lurasidone dose as needed. Risk D: Consider Therapy Modification

Macitentan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Macitentan. Risk C: Monitor

Maraviroc: CYP3A4 Inducers (Moderate) may decrease serum concentration of Maraviroc. Management: Increase maraviroc adult dose to 600 mg twice/day, but only if not receiving a strong CYP3A4 inhibitor. Not recommended for pediatric patients not also receiving a strong CYP3A4 inhibitor. Contraindicated in patients with CrCl less than 30 mL/min. Risk D: Consider Therapy Modification

Maribavir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Maribavir. Risk C: Monitor

Mavacamten: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mavacamten. Risk X: Avoid

Mavorixafor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mavorixafor. Risk C: Monitor

Mefloquine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mefloquine. Risk C: Monitor

Meperidine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Meperidine. CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Meperidine. Specifically, concentrations of normeperidine, the CNS stimulating metabolite, may be increased. Risk C: Monitor

Methadone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Methadone. Risk C: Monitor

MethylPREDNISolone: CYP3A4 Inducers (Moderate) may decrease serum concentration of MethylPREDNISolone. Risk C: Monitor

Mianserin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mianserin. Risk C: Monitor

Midazolam: CYP3A4 Inducers (Moderate) may decrease serum concentration of Midazolam. Risk C: Monitor

Midostaurin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Midostaurin. Risk C: Monitor

MiFEPRIStone: CYP3A4 Inducers (Moderate) may decrease serum concentration of MiFEPRIStone. Management: Avoid combined use in patients treated for Cushing's disease. When used for pregnancy termination, mifepristone efficacy may be reduced and an alternative pregnancy termination procedure may be warranted. Ensure a follow-up assessment after combined use. Risk D: Consider Therapy Modification

Mirodenafil: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mirodenafil. Risk C: Monitor

Mitapivat: May increase hepatotoxic effects of Lorlatinib. Lorlatinib may decrease serum concentration of Mitapivat. Mitapivat may decrease serum concentration of Lorlatinib. Management: Coadministration of lorlatinib and mitapivat should be avoided. If combined, increase the lorlatinib dose to 125 mg once daily and titrate mitapivat beyond 50 mg twice daily based on hemoglobin, if needed, to a maximum dose of 100 mg twice daily. Risk D: Consider Therapy Modification

Mobocertinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mobocertinib. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Mobocertinib. Risk X: Avoid

Montelukast: CYP3A4 Inducers (Moderate) may decrease serum concentration of Montelukast. Risk C: Monitor

Naldemedine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Naldemedine. Risk C: Monitor

Naloxegol: CYP3A4 Inducers (Moderate) may decrease serum concentration of Naloxegol. Risk C: Monitor

Neratinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Neratinib. Risk X: Avoid

Netupitant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Netupitant. Risk C: Monitor

Nevirapine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Nevirapine. Risk C: Monitor

NIFEdipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of NIFEdipine. Risk C: Monitor

Nilotinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Nilotinib. Risk C: Monitor

Nilvadipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Nilvadipine. Risk C: Monitor

NiMODipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of NiMODipine. Risk C: Monitor

Nintedanib: Inducers of CYP3A4 (Moderate) and P-glycoprotein may decrease serum concentration of Nintedanib. Risk X: Avoid

Nirogacestat: CYP3A4 Inducers (Moderate) may decrease serum concentration of Nirogacestat. Risk X: Avoid

Nisoldipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Nisoldipine. Risk X: Avoid

Olaparib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Olaparib. Risk X: Avoid

Oliceridine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Oliceridine. Risk C: Monitor

Olmutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Olmutinib. Risk C: Monitor

Olutasidenib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Olutasidenib. Risk X: Avoid

Omaveloxolone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Omaveloxolone. Risk X: Avoid

Osimertinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Osimertinib. Risk C: Monitor

OxyCODONE: CYP3A4 Inducers (Moderate) may decrease serum concentration of OxyCODONE. Risk C: Monitor

PACLitaxel (Conventional): CYP3A4 Inducers (Moderate) may decrease serum concentration of PACLitaxel (Conventional). Risk C: Monitor

PACLitaxel (Protein Bound): CYP3A4 Inducers (Moderate) may decrease serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor

Palbociclib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Palbociclib. Risk C: Monitor

Paliperidone: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Paliperidone. Management: Avoid coadministration of extended-release injectable paliperidone and P-gp inducers. If coadministration is required, consider use of paliperidone extended-release tablets, monitor for reduced paliperidone effects, and increase the dose as needed. Risk D: Consider Therapy Modification

Palovarotene: CYP3A4 Inducers (Moderate) may decrease serum concentration of Palovarotene. Risk X: Avoid

PAZOPanib: CYP3A4 Inducers (Moderate) may decrease serum concentration of PAZOPanib. Risk C: Monitor

Pemigatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pemigatinib. Risk X: Avoid

Perampanel: CYP3A4 Inducers (Moderate) may decrease serum concentration of Perampanel. Management: Increase perampanel starting dose to 4 mg/day if used with moderate CYP3A4 inducers. Increase perampanel dose by 2 mg/day no more than once weekly based on response and tolerability. Dose adjustments may be needed if the inducer is discontinued. Risk D: Consider Therapy Modification

Pimavanserin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pimavanserin. Risk X: Avoid

Piperaquine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Piperaquine. Risk C: Monitor

Pirtobrutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pirtobrutinib. Management: Avoid concomitant use if possible. If combined, if the current pirtobrutinib dose is 200 mg once daily, increase to 300 mg once daily. If current pirtobrutinib dose is 50 mg or 100 mg once daily, increase the dose by 50 mg. Risk D: Consider Therapy Modification

PONATinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of PONATinib. Risk C: Monitor

Pralsetinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pralsetinib. Management: If this combo cannot be avoided, increase pralsetinib dose from 400 mg daily to 600 mg daily; from 300 mg daily to 500 mg daily; and from 200 mg daily to 300 mg daily. Risk D: Consider Therapy Modification

Praziquantel: CYP3A4 Inducers (Moderate) may decrease serum concentration of Praziquantel. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for reduced praziquantel efficacy. If possible, stop the moderate CYP3A4 inducer 2 to 4 weeks before praziquantel initiation. Risk D: Consider Therapy Modification

PrednisoLONE (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of PrednisoLONE (Systemic). Risk C: Monitor

PredniSONE: CYP3A4 Inducers (Moderate) may decrease serum concentration of PredniSONE. Risk C: Monitor

Pretomanid: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pretomanid. Risk X: Avoid

Propacetamol: Lorlatinib may decrease serum concentration of Propacetamol. Risk C: Monitor

QUEtiapine: CYP3A4 Inducers (Moderate) may decrease serum concentration of QUEtiapine. Risk C: Monitor

QuiNIDine: CYP3A4 Inducers (Moderate) may decrease serum concentration of QuiNIDine. Risk C: Monitor

QuiNINE: CYP3A4 Inducers (Moderate) may decrease serum concentration of QuiNINE. Risk C: Monitor

Quizartinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Quizartinib. Risk X: Avoid

Ranolazine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ranolazine. Risk X: Avoid

Regorafenib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Regorafenib. CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Regorafenib. Risk C: Monitor

Relugolix, Estradiol, and Norethindrone: Inducers of CYP3A4 (Moderate) and P-glycoprotein may decrease serum concentration of Relugolix, Estradiol, and Norethindrone. Risk C: Monitor

Relugolix: Inducers of CYP3A4 (Moderate) and P-glycoprotein may decrease serum concentration of Relugolix. Risk C: Monitor

Repaglinide: CYP3A4 Inducers (Moderate) may decrease serum concentration of Repaglinide. Risk C: Monitor

Repotrectinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Repotrectinib. Risk X: Avoid

Revumenib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Revumenib. Risk X: Avoid

Ribociclib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ribociclib. Risk C: Monitor

Rilpivirine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Rilpivirine. Risk C: Monitor

Rimegepant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Rimegepant. Risk X: Avoid

Ripretinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ripretinib. Management: Avoid this combination if possible. If concomitant use is required, increase ripretinib to 150 mg twice daily. Decrease ripretinib to 150 mg once daily 14 days after stopping a moderate CYP3A4 inducer. Monitor patients for ripretinib response and toxicity Risk D: Consider Therapy Modification

RisperiDONE: CYP3A4 Inducers (Moderate) may decrease serum concentration of RisperiDONE. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of RisperiDONE. Risk C: Monitor

Ritlecitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ritlecitinib. Risk C: Monitor

Rivaroxaban: Inducers of CYP3A4 (Moderate) and P-glycoprotein may decrease serum concentration of Rivaroxaban. Risk C: Monitor

Roflumilast (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Roflumilast (Systemic). CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Roflumilast (Systemic). Risk C: Monitor

Rolapitant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Rolapitant. Risk C: Monitor

Samidorphan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Samidorphan. Risk C: Monitor

Selpercatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Selpercatinib. Risk X: Avoid

Selumetinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Selumetinib. Risk X: Avoid

Sertraline: CYP3A4 Inducers (Moderate) may decrease serum concentration of Sertraline. Risk C: Monitor

Sildenafil: CYP3A4 Inducers (Moderate) may decrease serum concentration of Sildenafil. Risk C: Monitor

Simeprevir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Simeprevir. Risk X: Avoid

Simvastatin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Simvastatin. Risk C: Monitor

Sirolimus (Conventional): CYP3A4 Inducers (Moderate) may decrease serum concentration of Sirolimus (Conventional). Risk C: Monitor

Sirolimus (Protein Bound): P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Sirolimus (Protein Bound). Risk X: Avoid

Sofosbuvir: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Sofosbuvir. Risk X: Avoid

Solriamfetol: May increase hypertensive effects of Hypertension-Associated Agents. Risk C: Monitor

Sonidegib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Sonidegib. Risk X: Avoid

SORAfenib: CYP3A4 Inducers (Moderate) may decrease serum concentration of SORAfenib. Risk C: Monitor

Sparsentan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Sparsentan. Risk C: Monitor

SUFentanil: CYP3A4 Inducers (Moderate) may decrease serum concentration of SUFentanil. Risk C: Monitor

SUNItinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of SUNItinib. Risk C: Monitor

Suvorexant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Suvorexant. Risk C: Monitor

Suzetrigine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Suzetrigine. Risk X: Avoid

Tacrolimus (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Tacrolimus (Systemic). Risk C: Monitor

Tadalafil: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tadalafil. Risk C: Monitor

Tamoxifen: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tamoxifen. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Tamoxifen. Risk C: Monitor

Tasimelteon: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tasimelteon. Risk C: Monitor

Tazemetostat: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tazemetostat. Risk X: Avoid

Temsirolimus: CYP3A4 Inducers (Moderate) may decrease serum concentration of Temsirolimus. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Temsirolimus. Specifically, sirolimus concentrations may be decreased. Risk C: Monitor

Teniposide: CYP3A4 Inducers (Moderate) may decrease serum concentration of Teniposide. Risk C: Monitor

Tenofovir Alafenamide: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Tenofovir Alafenamide. Management: Consider alternatives to the use of P-gp inducers with tenofovir alafenamide. If combined, monitor for reduced tenofovir alafenamide concentrations and efficacy, and for the development of resistance. Risk D: Consider Therapy Modification

Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor

Tetrahydrocannabinol: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tetrahydrocannabinol. Risk C: Monitor

Tezacaftor and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tezacaftor and Ivacaftor. Risk C: Monitor

Thiotepa: CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Thiotepa. CYP3A4 Inducers (Moderate) may decrease serum concentration of Thiotepa. Risk C: Monitor

Ticagrelor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ticagrelor. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Ticagrelor. Risk C: Monitor

Tivozanib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tivozanib. Risk C: Monitor

Tofacitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tofacitinib. Risk C: Monitor

Tolvaptan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tolvaptan. Risk C: Monitor

Toremifene: CYP3A4 Inducers (Moderate) may decrease serum concentration of Toremifene. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Toremifene. Risk C: Monitor

Trabectedin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Trabectedin. Risk C: Monitor

TraMADol: CYP3A4 Inducers (Moderate) may decrease serum concentration of TraMADol. Risk C: Monitor

TraZODone: CYP3A4 Inducers (Moderate) may decrease serum concentration of TraZODone. Risk C: Monitor

Tretinoin (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Tretinoin (Systemic). Risk C: Monitor

Triazolam: CYP3A4 Inducers (Moderate) may decrease serum concentration of Triazolam. Risk C: Monitor

Ubrogepant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a moderate CYP3A4 inducer. Risk D: Consider Therapy Modification

Ulipristal: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ulipristal. Risk X: Avoid

Upadacitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Upadacitinib. Risk C: Monitor

Valbenazine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Valbenazine. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Valbenazine. Risk C: Monitor

Vandetanib: CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Vandetanib. CYP3A4 Inducers (Moderate) may decrease serum concentration of Vandetanib. Risk C: Monitor

Vanzacaftor, Tezacaftor, and Deutivacaftor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vanzacaftor, Tezacaftor, and Deutivacaftor. Risk X: Avoid

Velpatasvir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Velpatasvir. Risk X: Avoid

Vemurafenib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vemurafenib. Risk C: Monitor

Venetoclax: CYP3A4 Inducers (Moderate) may decrease serum concentration of Venetoclax. Risk X: Avoid

Verapamil: CYP3A4 Inducers (Moderate) may decrease serum concentration of Verapamil. Risk C: Monitor

Vilazodone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vilazodone. Risk C: Monitor

VinCRIStine: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of VinCRIStine. Risk X: Avoid

Vitamin K Antagonists: CYP2C9 Inducers (Weak) may decrease serum concentration of Vitamin K Antagonists. Risk C: Monitor

Voclosporin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Voclosporin. Risk X: Avoid

Vonoprazan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vonoprazan. Risk X: Avoid

Vorapaxar: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vorapaxar. Risk X: Avoid

Vortioxetine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vortioxetine. Risk C: Monitor

Voxelotor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and moderate CYP3A4 inducers. If unavoidable, increase the voxelotor dose to 2,000 mg once daily. For children ages 4 to less than 12 years, weight-based dose adjustments are required. See full monograph for details. Risk D: Consider Therapy Modification

Voxilaprevir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Voxilaprevir. Risk X: Avoid

Zaleplon: CYP3A4 Inducers (Moderate) may decrease serum concentration of Zaleplon. Risk C: Monitor

Zanubrutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Zanubrutinib. Management: Avoid this combination if possible. If coadministration of zanubrutinib and a moderate CYP3A4 inducer is required, increase the zanubrutinib dose to 320 mg twice daily. Risk D: Consider Therapy Modification

Zolpidem: CYP3A4 Inducers (Moderate) may decrease serum concentration of Zolpidem. Risk C: Monitor

Zopiclone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Zopiclone. Risk C: Monitor

Zuranolone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Zuranolone. Risk X: Avoid

Reproductive Considerations

Evaluate pregnancy status prior to initiating therapy in patients who could become pregnant. Patients who could become pregnant should avoid pregnancy and use an effective nonhormonal method of contraception during treatment and for at least 6 months after the final lorlatinib dose. Patients with partners who could become pregnant should use effective contraception during treatment and for at least 3 months after the last lorlatinib dose.

Pregnancy Considerations

Based on the mechanism of action and data from animal reproduction studies, in utero exposure to lorlatinib may cause fetal harm.

Breastfeeding Considerations

It is not known if lorlatinib is present in breast milk.

Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer does not recommend breastfeeding during therapy and for 7 days after the last lorlatinib dose.

Monitoring Parameters

ALK positivity (in tumor specimen) or ROS1 positivity (off-label use). Monitor serum cholesterol and triglycerides (prior to initiating lorlatinib, at 1 and 2 months after lorlatinib initiation, and periodically thereafter); LFTs (as clinically indicated); fasting serum glucose (prior to initiating lorlatinib and periodically thereafter). Evaluate pregnancy status (prior to treatment in patients who could become pregnant). Monitor ECG (prior to lorlatinib initiation and periodically thereafter) and BP (2 weeks after lorlatinib initiation and at least monthly thereafter). Promptly evaluate new or worsening respiratory symptoms indicative of interstitial lung disease/pneumonitis (eg, dyspnea, cough, fever). Monitor for signs/symptoms of CNS adverse events. Monitor adherence.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Additional cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]; ESC [Lyon 2022]). Consider home BP monitoring; assess cholesterol profile every 3 to 6 months (ESC [Lyon 2022]).

Mechanism of Action

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 (Shaw 2017). Lorlatinib has antitumor activity against multiple mutant forms of the ALK enzyme, including some mutations detected in tumors at the time of disease progression on crizotinib and other ALK inhibitors. 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 (Adult Data Unless Noted)

Absorption: Rapid (Shaw 2017).

Distribution: Vss: 305 L.

Protein binding: 66%; to plasma proteins.

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

Bioavailability: 81%.

Half-life elimination: 24 hours.

Time to peak: Median: 1.2 hours (range: 0.5 to 4 hours) following a single dose; 2 hours (range: 0.5 to 23 hours) at steady state.

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

Clearance (CL/F): 11 L/hour following a single dose; 18 L/hour at steady state.

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: Following a single 100 mg dose, AUC increased by 42% in subjects with severe renal impairment, compared to subjects with normal renal function.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Lorbrena | Lorbrexen;
  • (AR) Argentina: Tigify;
  • (AT) Austria: Lorviqua;
  • (AU) Australia: Lorviqua;
  • (BE) Belgium: Lorviqua;
  • (BG) Bulgaria: Lorviqua;
  • (BR) Brazil: Lorbrena;
  • (CH) Switzerland: Lorviqua;
  • (CL) Chile: Lorbrena;
  • (CZ) Czech Republic: Lorviqua;
  • (DE) Germany: Lorviqua;
  • (EC) Ecuador: Lorbrena;
  • (EE) Estonia: Lorviqua;
  • (ES) Spain: Lorviqua;
  • (FI) Finland: Lorviqua;
  • (FR) France: Lorviqua;
  • (GB) United Kingdom: Lorviqua;
  • (GR) Greece: Lorviqua;
  • (HU) Hungary: Lorviqua;
  • (ID) Indonesia: Lorlak;
  • (IE) Ireland: Lorviqua;
  • (IN) India: Lorbriqua;
  • (IT) Italy: Lorviqua;
  • (JP) Japan: Lorbrena;
  • (KR) Korea, Republic of: Lorviqua;
  • (KW) Kuwait: Lorbrena;
  • (LB) Lebanon: Lorbrena;
  • (LT) Lithuania: Lorviqua;
  • (LV) Latvia: Lorviqua;
  • (MX) Mexico: Lorbrena;
  • (MY) Malaysia: Lorviqua;
  • (NL) Netherlands: Lorviqua;
  • (NO) Norway: Lorviqua;
  • (PL) Poland: Lorviqua;
  • (PR) Puerto Rico: Lorbrena;
  • (PT) Portugal: Lorviqua;
  • (QA) Qatar: Lorbrena;
  • (RO) Romania: Lorviqua;
  • (SA) Saudi Arabia: Lorbrena;
  • (SE) Sweden: Lorviqua;
  • (SG) Singapore: Lorviqua;
  • (SI) Slovenia: Lorviqua;
  • (SK) Slovakia: Lorviqua;
  • (TR) Turkey: Lorviqua;
  • (TW) Taiwan: Lorbrena | Lorviqua;
  • (ZA) South Africa: Lorbrena
  1. Armenian SH, Lacchetti C, Barac A, et al. Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2017;35(8):893-911. doi:10.1200/JCO.2016.70.5400 [PubMed 27918725]
  2. Hodson L, Ovesen J, Couch J, et al; US Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. Managing hazardous drug exposures: information for healthcare settings, 2023. https://doi.org/10.26616/NIOSHPUB2023130. Updated April 2023. Accessed December 27, 2024.
  3. Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
  4. Lorbrena (lorlatinib) [prescribing information]. New York, NY: Pfizer; August 2024.
  5. Lorbrena (lorlatinib) [product monograph]. Kirkland, Quebec, Canada: Pfizer Canada ULC; May 2022.
  6. Lyon AR, López-Fernández T, Couch LS, et al; ESC Scientific Document Group. 2022 ESC guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43(41):4229-4361. doi:10.1093/eurheartj/ehac244 [PubMed 36017568]
  7. Ovesen JL, Sam­mons D, Connor TH, et al; US Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. NIOSH list of hazardous drugs in healthcare settings, 2024. https://doi.org/10.26616/NIOSHPUB2025103. Updated December 18, 2024. Accessed December 20, 2024.
  8. Owen DH, Ismaila N, Ahluwalia A, et al. Therapy for stage IV non-small cell lung cancer with driver alterations: ASCO living guideline, version 2024.3. J Clin Oncol. 2025;43(10):e2-e16. doi:10.1200/JCO-24-02785 [PubMed 40014839]
  9. Shaw AT, Bauer TM, de Marinis F, et al; CROWN Trial Investigators. First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer. N Engl J Med. 2020;383(21):2018-2029. doi:10.1056/NEJMoa2027187 [PubMed 33207094]
  10. Shaw AT, Felip E, Bauer TM, et al. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol. 2017;18(12):1590-1599. [PubMed 29074098]
  11. Shaw AT, Solomon BJ, Chiari R, et al. Lorlatinib in advanced ROS1-positive non-small-cell lung cancer: a multicentre, open-label, single-arm, phase 1-2 trial. Lancet Oncol. 2019;20(12):1691-1701. doi:10.1016/S1470-2045(19)30655-2 [PubMed 31669155]
  12. Solomon BJ, Liu G, Felip E, et al. Lorlatinib versus crizotinib in patients with advanced ALK-positive non-small cell lung cancer: 5-year outcomes from the phase III CROWN study. J Clin Oncol. 2024;42(29):3400-3409. doi:10.1200/JCO.24.00581 [PubMed 38819031]
  13. United States Pharmacopeia. <800> Hazardous Drugs—Handling in Healthcare Settings. In: USP-NF. United States Pharmacopeia; July 1, 2020. Accessed January 16, 2025. doi:10.31003/USPNF_M7808_07_01
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