In June 2017, the U.S. Food and Drug Administration (FDA) approved Rituxan Hycela™, a combination of rituximab and hyaluronidase, for subcutaneous administration in the treatment of follicular lymphoma and diffuse large B-cell lymphoma as well as chronic lymphocytic leukemia (CLL). This agent affords the same clinical benefit as IV rituximab, but in much less time. With this approval comes many questions about which patients are appropriate and administration considerations for subcutaneous rituximab and hyaluronidase.

Differences Between the Agents

Rituximab, a monoclonal antibody that commonly results in infusion reactions, has historically been given via IV and titrated over time, so nurses can intervene in the event of a reaction. For that reason, patients must have received one full dose of IV rituximab without event before being considered for treatment with rituximab and hyaluronidase. Premedication with acetaminophen and an antihistamine, and possibly a glucocorticoid, is still recommended as part of treatment.

Dosing presents another key difference, because with the combination, subcutaneous agent, dosing is not based on body surface area as we’ve become accustomed to with IV rituximab but instead is standardized and uniform. Recommended dosing for lymphomas is 1,400 mg rituximab/23,400 units hyaluronidase, and for CLL, 1,600 mg rituximab/26,800 units hyaluronidase are used.

The addition of hyaluronidase helps with local absorption and distribution of the rituximab, because hyaluronidase has been used successfully for years in the setting of vesicant extravasation. The addition of this agent accounts for the fact that the recommended doses will mean the volume in the syringe will be 11.7 ml for lymphoma doses and 13.4 ml for leukemia doses—much more than what nurses are accustomed to or even comfortable giving in one subcutaneous injection. Hyaluronidase works by increasing the permeability of subcutaneous tissue by temporarily depolarizing hyaluronan and allowing for more volume to be administered at the site.

Administration Considerations

Manufacturers recommend using a 20 cc syringe and attaching a needle to the syringe immediately prior to administration to avoid clogging. Because it’s the only site with clinical data, administration  into abdominal subcutaneous tissue is recommended. Administration should take place over five minutes for the lymphoma doses and seven minutes for CLL. Administration recommendations have been made to apply gentle, even pressure on the syringe with the palm of the hand to ensure a constant flow at the rate of 2 ml/minute and to have a timing device available to assist with consistent administration. As with IV administration, nurses should stop administering subcutaneous rituximab and hyaluronidase immediately after noticing any type of reaction, including hypersensitivity.

Patients require monitoring for 15 minutes following administration but should be taught to expect some degree of injection site pain, swelling, or induration and to report any more severe symptoms that occur at home.

Most common side effects are infection and myelosuppression, constipation, nausea, and fatigue. Other rare but serious events are mucocutaneous reactions and hepatitis B reactivation. Providers should perform thorough skin and oral assessments prior to and during treatment, know a patients’ hepatitis B viral status prior to administration, and understand that if patients have had the virus, activation is a possibility. Although it’s rare, primary multifocal leukoencephalopathy is a serious complication, and patients must be monitored vigilantly for mental status changes. Other serious complications include hypersensitivity, tumor lysis syndrome, infection, cardiac arrhythmias, renal toxicity, and bowel obstruction.

Reducing administration times of rituximab administration from hours to minutes carries great implications on quality of life as well as access to and cost of care for a medication that is given frequently for hematologic malignancies. Subcutaneous rituximab and hyaluronidase represents just one of many advancements in cancer treatment options that make oncology nursing such a challenging and evolving field.

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