Minimization of administration route errors with subcutaneous rituximab

The subcutaneous formulation of rituximab (MabThera® SC) has recently been subject to assessment by the Scottish Medicines Consortium and subsequently advice relating to the restricted use of this new formulation has been published. ¹ The advice refers to the use of both the intravenous and subcutaneous formulations of rituximab.

In light of the increasing focus on patient safety and the avoidance of incidents, steps are suggested which aim to ensure that the care provided is as safe as possible. ² One of these steps is risk management assessment, and with this in mind we find it appropriate to acknowledge the potential for risk relating to medication route errors.

The use of the anti-CD20 monoclonal antibody rituximab is well established in clinical practice and is standard care for patients with follicular lymphoma ³ and diffuse large B-cell lymphomas. ⁴ Traditionally, however, this has been given as an intravenous (IV) infusion. The SC formulation of rituximab was approved by the European Commission in March 2014, and once launched, there is potential for both formulations to be present in the same clinical area, be it a pharmacy or hospital ward.

There are two potential scenarios for medication route error: IV administration of the SC formulation and SC administration of the IV formulation.

In the first scenario, IV administration of the SC formulation may result from an error in the preparation of the drug or an inadvertent administration by the IV (or intramuscular) route. In either case, patients are potentially exposed to a rapid infusion rate of rituximab which may result in an increased risk of infusion-related reactions such as tumour lysis syndrome or cytokine release syndrome, events which are most likely to occur during a patient’s first exposure to rituximab (MabThera® SC is not licensed for use as the first dose of rituximab).

Accidental use of the SC formulation for IV administration would mean that the total administered dose of rituximab is higher than intended, and that the patient is systemically exposed to the recombinant human hyaluronidase (rHuPH20) excipient used to assist in drug absorption. ⁵ IV-administered hyaluronidase is associated with a short serum half-life (5–10 min), and thus the risk of systemic effects would be expected to be remote. In the second scenario – SC administration of the IV formulation – detection may be more rapid due to the large volume of the IV formulation and the difficulty of SC administration without the rHuPH20 excipient. In this scenario the patient may have a localized reaction, and the total dose administered may be lower than intended; while such a dose may not pose any immediate risk to the patient, an ineffective dose would be administered if the error was not detected.

Measures have been implemented by Roche to aid the correct selection of rituximab formulation and allow clear differentiation.

MabThera® SC is ready to use; the SC injection vial contains 11.7 ml of sterile, non-pyrogenic and preservative-free solution, and the whole content of the vial (1400 mg rituximab in 11.7 ml) should be injected into the patient. SC vial labels have ‘For subcutaneous use only’, ‘solution for subcutaneous injection’ and ‘SC’ written in red text, and the flip-off cap is pink (the colour cap always matches the colour band).

The IV infusion vials are available in two sizes: 100 mg in 10 ml ‘concentrate for solution for infusion’, with an orange cap, and 500 mg in 50 ml ‘concentrate for solution for infusion’, with a grey cap. The content is to be diluted in either 0.9% NaCl or 5% glucose, and administered by IV infusion. The total dose, and therefore volume for infusion, are dependant on the patient’s body surface area. On the external packaging the route of administration, strength and indication will be clearly specified. The carton size will also be unique depending on the formulation.

The SC and IV formulations are covered by separate ‘Summary of Product Characteristics’ and ‘Patient Information’ leaflets,^6–9 with corresponding prescribing information. Additional educational materials for patients, nurses and pharmacists, comprising a comparison card and step-by-step administration instructions, are already available in countries where rituximab SC has been launched. These will be distributed to physicians, nurses and hospital pharmacies, etc. by the Roche local affiliate in order to (1) promote visual familiarity with the two formulations to reinforce differentiation, and (2) give specific and detailed administration instructions to healthcare professionals on the safe and optimized use of the SC formulation.

Other suggested measures to limit potential medication route errors include separate storage of IV and SC formulations within the pharmacy department or clinical setting (separate refrigerators or areas in the refrigerator), retention of the empty rituximab vial with the rituximab preparation for checking prior to administration and adherence to local procedures in the appropriate checking of drugs – from prescription through to preparation and administration – by the various staff involved in these processes.

It is hoped that by highlighting the potential for medication route errors, healthcare professionals working with these drugs are aware and sensitized to the possible issues and can take appropriate steps to minimize and avoid such errors.