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Does Lorlatinib Interact with Rifampin?

Lorlatinib and Rifampin have a contraindicated drug interaction according to U.S. FDA drug labeling data. Severe hepatotoxicity occurred in healthy subjects receiving lorlatinib with rifampin (a strong CYP3A inducer). Grade 3-4 ALT/AST increases occurred in 83% of subjects. The mechanism involves cyp3a induction and pxr agonism activation by both drugs. Patients taking both medications should consult their healthcare provider before starting, stopping, or changing the dosage of either drug. This information is based on official FDA drug labeling sourced from OpenFDA and the NIH National Library of Medicine.

Severity
Contraindicated
Lorlatinib Class
Kinase Inhibitor
Rifampin Class
Rifamycin Antibacterial
Management
Do not take together
Data Source
U.S. FDA via OpenFDA

How This Interaction Works

The interaction between Lorlatinib and Rifampin occurs because cyp3a induction and pxr agonism activation by both drugs. Clinically, this means severe hepatotoxicity occurred in healthy subjects receiving lorlatinib with rifampin (a strong cyp3a inducer). grade 3-4 alt/ast increases occurred in 83% of subjects. Because of the severity of this interaction, these medications are contraindicated — meaning they should not be taken together under any circumstances. If you are currently taking both, contact your healthcare provider immediately to discuss alternatives.

What To Tell Your Doctor or Pharmacist

If you are taking Lorlatinib and your doctor is considering prescribing Rifampin (or vice versa), make sure to:

  • Inform your doctor and pharmacist of all current medications, including over-the-counter drugs and supplements
  • Ask whether the benefits of combining these medications outweigh the risks for your specific situation
  • Ask what symptoms to watch for that would indicate the interaction is causing problems
  • Ask about alternative medications that do not interact with your current regimen
  • Ask how frequently you should be monitored while these are co-prescribed
  • Never stop or change either medication without first consulting your healthcare provider
💊 Lorlatinib(Lorbrena)+💊 Rifampin(Rifampin)

Severity & Interaction Details

⛔
contraindicated
Avoid this combination
FDA labeling lists this pair as contraindicated. The risk outweighs the benefit in nearly all cases.
Severity scale
MinorContra
On record
Yes
Drug A class
Kinase Inhibitor
Drug B class
Rifamycin Antibacterial
Source
NLP:lorlatinib

What this means in plain English

Severe hepatotoxicity occurred in healthy subjects receiving lorlatinib with rifampin (a strong CYP3A inducer). Grade 3-4 ALT/AST increases occurred in 83% of subjects.

What the FDA label says

"CYP3A induction and PXR agonism activation by both drugs"

📖 Source: NLP:lorlatinib

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Data sourced from U.S. FDA drug labeling via openFDA and the NIH National Library of Medicine. For informational purposes only. Always consult your pharmacist or physician.