Drug interactions
Lorlatinib + Posaconazole
Severity: Major
Lorlatinib and Posaconazole: major interaction.
Last updated Sources: US FDA label
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Posaconazole, a strong CYP3A inhibitor, increases lorlatinib exposure. This raises the risk of hyperlipidemia, CNS effects such as mood or cognitive changes, and PR interval prolongation.
What this interaction means in plain words
Lorlatinib and Posaconazole can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for.
Lorlatinib belongs to Oncology; Posaconazole belongs to Anti Fungals.
Why it happens
Posaconazole inhibits CYP3A4, the main metabolic pathway of lorlatinib, increasing its plasma concentrations.
What to do
Use an alternative antifungal if possible. If unavoidable, reduce the lorlatinib dose per labeling (for example 100 mg to 75 mg daily) and monitor lipids, ECG and neuropsychiatric symptoms; restore the prior dose after the inhibitor has been stopped for about three half-lives.
What to ask your pharmacist
- Does the benefit of taking both outweigh the risk in my case?
- Do I need any blood test, ECG or other check while on both?
- What early warning signs should I watch for, and what should I do if they appear?
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References
Other interactions of Posaconazole
- Artemether + Posaconazole Contraindicated
- Avanafil + Posaconazole Contraindicated
- Cobimetinib + Posaconazole Contraindicated
- Conivaptan + Posaconazole Contraindicated
- Dihydroergotamine intranasal + Posaconazole Contraindicated
- Dihydroergotamine + Posaconazole Contraindicated
Other interactions of Lorlatinib
- Amobarbital + Lorlatinib Contraindicated
- Apalutamide + Lorlatinib Contraindicated
- Butabarbital + Lorlatinib Contraindicated
- Carbamazepine + Lorlatinib Contraindicated
- Enzalutamide + Lorlatinib Contraindicated
- Fosphenytoin + Lorlatinib Contraindicated
Frequently asked questions
Can I take Lorlatinib with Posaconazole?
MediHelp rates the interaction as major. Lorlatinib and Posaconazole can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for. Posaconazole, a strong CYP3A inhibitor, increases lorlatinib exposure. This raises the risk of hyperlipidemia, CNS effects such as mood or cognitive changes, and PR interval prolongation.
How serious is the interaction between Lorlatinib and Posaconazole?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Use an alternative antifungal if possible. If unavoidable, reduce the lorlatinib dose per labeling (for example 100 mg to 75 mg daily) and monitor lipids, ECG and neuropsychiatric symptoms; restore the prior dose after the inhibitor has been stopped for about three half-lives.
What other medicines interact with Posaconazole?
MediHelp also lists interactions of Posaconazole with, for example, Artemether, Avanafil, Cobimetinib. The full list is on the Posaconazole page.
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