Paclitaxel formulations (conventional and nab-paclitaxel): caution required due to potential for medication error

Albumin-bound paclitaxel formulations for infusion (nab-paclitaxel; brand names Abraxane, Pazenir) differ from conventional paclitaxel medicines in their authorised indications, pharmacokinetics, recommended dosages, and preparation and administration instructions. Healthcare professionals should use caution when prescribing, dispensing, preparing, and administering any paclitaxel formulations to prevent medication errors, which have the potential to cause harm.

From:
Medicines and Healthcare products Regulatory Agency
Published
18 January 2022
Therapeutic area:
Cancer

Advice for healthcare professionals:

  • compared with conventional formulations, paclitaxel medicines formulated as albumin-bound nanoparticles (nab-paclitaxel; brand names Abraxane, Pazenir) have different authorised indications, pharmacokinetics, dosages, and preparation and administration instructions
  • conventional paclitaxel and nab-paclitaxel formulations are not interchangeable
  • although we have not received reports to suggest harm has occurred in the UK due to a mix-up of these paclitaxel formulations, errors in dosing or administration could have potential consequences for clinical response and increased toxicity or adverse reactions during cancer treatment
  • make a clear distinction between paclitaxel formulations when prescribing, dispensing, administering, and communicating about these medicines – use of brand names is advised for nab-paclitaxel formulations
  • verify the product name and dose before administration and ensure the specific SmPC instructions are followed for preparation and administration
  • report suspected adverse drug reactions, including medication error with associated harm to a patient, to the Yellow Card scheme

Formulations of paclitaxel

Paclitaxel is a member of the taxane group of chemotherapy drugs. Paclitaxel has been available as an anti-cancer medicine since 1993, including under the brand name Taxol. Paclitaxel is indicated for treatment of certain cancers of the ovary, breast, and lung, as well as advanced AIDS-related Kaposi’s sarcoma – see example Summary of Product Characteristics (SmPC).

Abraxane was licensed in 2008 and is formulated as paclitaxel bound to albumin in nanoparticles (nab-paclitaxel). Pazenir was authorised in 2019 as bioequivalent to Abraxane. Abraxane and Pazenir are indicated for treatment of certain cancers of the breast, pancreas, and lung – see SmPCs for Abraxane and Pazenir for details.

The two nab-paclitaxel medicines are licensed as bioequivalent to each other, but have substantially different properties compared with conventional formulations of paclitaxel. As such, there is a warning in the product information and on the packaging for both Abraxane and Pazenir that they should not be substituted for or with other paclitaxel formulations.

Binding of the paclitaxel to albumin in nanoparticles changes how the medicine is transported across cells. As such, recommended doses and administration times are notably different than those for conventional paclitaxel infusions. For example, Abraxane and Pazenir are generally administered intravenously over a 30-minute period, whereas the instructions for conventional paclitaxel are to administer intravenously over a period of 3 hours. Other differences in pharmacokinetic parameters include the plasma clearance rate and volume of distribution.

Concerns about the potential for medication error

A healthcare organisation recently contacted the MHRA to enquire whether the packaging of a nab-paclitaxel medicine should more clearly state the formulation. Inadvertent administration of a different paclitaxel formulation could result in a higher dose than intended with increased toxicity, or sub-dosing with subtherapeutic effects. Nab-paclitaxel may be recommended in patients who have developed hypersensitivity to paclitaxel.[footnote 1] As such, mix-ups between the two types of formulations may also present the risk of a hypersensitivity reaction, in addition to the risk of underdosing or overdosing.

As of September 2021, we had not received any cases reported to the Yellow Card scheme for Abraxane and Pazenir suggesting a mix-up with conventional formulations associated with patient harm. Cases of medication error resulting in harm are not always reported to the Yellow Card scheme, and we encourage healthcare professionals to report cases if they occur.

We are working with manufacturers to optimise the safety of these products. In the meantime, we issue this communication on a precautionary basis. We ask healthcare professionals to remain vigilant around these medicines.

Report suspected reactions on a Yellow Card

Suspected adverse drug reactions (ADR) should be reported to the Yellow Card scheme.

Healthcare professionals, patients, and caregivers are asked to submit reports using the Yellow Card scheme electronically using:

Adverse drug reactions where harm occurs as a result of a medication error are reportable as a Yellow Card or through the local risk management systems into the National Reporting and Learning System (NRLS). If reported to the NRLS, these will be shared with the MHRA. If the NRLS is not available and harm occurs, report using a Yellow Card.

Report suspected side effects to medicines, vaccines, medical device and test kit incidents used in coronavirus (COVID-19) testing and treatment using the dedicated Coronavirus Yellow Card reporting site or the Yellow Card app. See the MHRA website for the latest information on medicines and vaccines for COVID-19.

Article citation: Drug Safety Update volume 15, issue 6: January 2022: 2.

  1. NHS England. National Cancer Drugs Fund list. Version 1.193; page 108. Accessed by the MHRA 21 October 2021. ↩

Published 18 January 2022
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