Interactions with other medications

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I am... associated with a low risk of drug-drug interactions vs. azoles1‑7

Azoles are contraindicated or require dose adjustments when used concomitantly with a range of drugs which are frequently used in patients at high risk of IFIs1‑5

The CYP3A4 enzyme metabolises a wide range of drugs in the liver. As inhibitors of CYP3A4, azoles exhibit a large variety of DDIs when co-administered with CYP3A4 substrates3‑5,8,9

Potentially high plasma concentrations of CYP3A4 substrates upon co-administration with azoles can lead to problematic increases in toxicity3,4,10

Considerations for patients with haematological disorders

Several azoles are potent inhibitors of CYP3A4, meaning that co-administration with FLT-3 inhibitors or some chemotherapy agents (e.g. vinca alkaloids) is likely to increase plasma concentration of the substrates, potentially leading to nephrotoxicity and other serious adverse reactions.1,11‑13

AmBisome® is not contraindicated when initiated with concomitant FLT-3 inhibitors or chemotherapy agents, as its active ingredient, amphotericin B, is not metabolised by hepatic CYP450 enzymes.*6

Monitoring outcomes such as renal, hepatic, and electrolyte functioning is recommended to avoid toxicity.6

Considerations for patients with HIV/AIDS

Co-administration of several azoles with antiviral drugs (e.g. ritonavir) can result in significant decrease in plasma concentration of the azole or increase in concentration of the antiviral drug, leading to potential adverse events and reduced efficacy.3,14

*No specific interaction studies have been performed with liposomal amphotericin B. Potential pharmacodynamic DDIs may occur with the use of concurrent nephrotoxic medications, corticosteroids, corticotropin, diuretics, digitalis, other antifungals, antineoplastic agents, skeletal muscle relaxants and leukocyte transfusions. Please refer to the SmPC for full information on the potential DDIs.6

This table is an illustrative example based on SmPCs. This table does not constitute a clinical recommendation; clinicians should refer to their local prescribing information for individual country variations and specific details on dosing and potential drug-drug interactions (DDIs).

Please refer to the AmBisome® SmPC and the SmPC of concomitant medications prior to prescribing to ensure minimal interaction.3‑6,11‑13

Disease area
Antifungal HSCT/SOT Haematology HIV
Immunosuppressants CMV prophylaxis FLT-3 inhibitors Chemotherapy Antivirals
AmBisome® Disease area HSCT/SOT Immunosuppressants CMV prophylaxis Haematology FLT-3 inhibitors Chemotherapy HIV Antivirals
Voriconazole Disease area HSCT/SOT Immunosuppressants CMV prophylaxis Haematology FLT-3 inhibitors Chemotherapy HIV Antivirals
Posaconazole Disease area HSCT/SOT Immunosuppressants CMV prophylaxis Haematology FLT-3 inhibitors Chemotherapy HIV Antivirals
Isavuconazole Disease area HSCT/SOT Immunosuppressants CMV prophylaxis Haematology FLT-3 inhibitors Chemotherapy HIV Antivirals

Contraindications, not recommended or avoid co-administration**

Caution/monitoring or dose adjustment required

No DDIs stated/theoretical risk only

**Contraindicated for at least 1 drug in this class.

Take on IFIs with confidence with AmBisome®'s few reported clinically relevant DDIs vs. azoles1‑6

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CMV: cytomegalovirus; DDIs: drug-drug interactions; FLT-3: fms-like tyrosine kinase 3; HSCT: haematopoietic stem cell transplantation; IFIs: invasive fungal infections; SOT: solid organ transplantation.

References:

  1. Youngs J et al. J Fungi (Basel). 2020;6(4):385.
  2. Jenks J et al. Med Mycol. 2019;57(2):S168–S178.
  3. European Medicines Agency (EMA). Vfend (voriconazole) Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/vfend-epar-productinformation_en.pdf. [Last accessed: April 2022].
  4. European Medicines Agency (EMA). Noxafil (posaconazole) Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/noxafil-epar-productinformation_en.pdf. [Last accessed: April 2022].
  5. European Medicines Agency (EMA). Cresemba (isavuconazole) Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/cresemba-eparproduct-information_en.pdf. [Last accessed: April 2022].
  6. AmBisome® Summary of Product Characteristics (UK). Available at: https://www.medicines.org.uk/emc/product/1022/smpc#gref. [Last accessed: April 2022].
  7. Vadlapatla RK et al. Expert Opin Drug Metab Toxicol. 2014;10(4):561–580.
  8. Bruggemann RJM et al. Clin Infect Dis. 2009;48:1441–1458.
  9. Jordan CL et al. Pediatric Pulmonary. 2016;51(S44):S61–S70.
  10. Madsen ML et al. Cancer Chemother Pharmacol. 2019;84:471–485.
  11. European Medicines Agency (EMA). Imbruvica (ibrutinib) Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/imbruvica-eparproduct-information_en.pdf. [Last accessed: April 2022].
  12. European Medicines Agency (EMA). Rydapt (midostaurin) Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/rydapt-epar-productinformation_en.pdf. [Last accessed: April 2022].
  13. European Medicines Agency (EMA). Xospata (gilteritinib) Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/xospata-eparproduct-information_en.pdf. [Last accessed: April 2022].
  14. Chastain DB et al. Curr Infect Dis Rep. 2017;19:36.

Job code: IHQ-AMB-0533
Date of Preparation: April 2022