What do other institutions have in place for rituxan ordering restrictions for inpatient.

Comment by InpharmD Researcher

There is limited published literature describing institutional inpatient rituximab ordering restrictions, with most evidence focusing on outcomes rather than the restriction criteria themselves. Limited retrospective data suggest that institutions generally reserve inpatient rituximab administration for clinically necessary or urgent situations while preferring outpatient administration when feasible. Reported restriction strategies include limiting prescribing to designated specialists, requiring departmental or non-formulary approval, implementing predefined criteria-for-use algorithms, and reviewing factors such as the indication, urgency, supporting evidence, insurance coverage, and anticipated outpatient continuation before approving inpatient administration. Available studies suggest these approaches may reduce inpatient rituximab use and hospital drug expenditures while standardizing the review process. However, the published literature provides limited detail regarding how individual institutions operationalize inpatient rituximab restriction policies, limiting comparisons across institutions.

A PubMed and Google Scholar search was conducted using combinations of the terms “rituximab,” “Rituxan,” “inpatient,” “ordering restriction,” “restricted antineoplastic,” “non-formulary,” “criteria for use,” and “hospital policy.” Four relevant studies describing institutional policies or approval processes for inpatient rituximab or other outpatient-restricted antineoplastic medications were identified.

Background

A University Hospitals Birmingham protocol restricts rituximab prescribing for immune-mediated renal and systemic inflammatory diseases to renal consultants and designated rheumatology consultants within combined renal/rheumatology clinics. Patients receiving rituximab as a day case must have a formal day-case admission and completed treatment pathway documentation. The protocol requires documented informed consent, screening for hepatitis B/C, HIV, varicella-zoster, and tuberculosis before treatment, completion of an initial authorization, and a pre-administration checklist confirming no contraindications or active infection prior to each infusion. Rituximab administration may be deferred at the treating physician's discretion in patients with infection or a low white blood cell count. [1]

Literature Review

A search of the published medical literature revealed 4 studies investigating the researchable question:

What do other institutions have in place for rituxan ordering restrictions for inpatient.

Level of evidence

C - Multiple studies with limitations or conflicting results Read more→

Please see Tables 1-4 for your response.

Evaluation of the use of non-formulary oncology medications restricted to outpatient use in hospitalized patients after implementation of a criteria-for-use algorithm
Design	Multicenter, retrospective, cost-evaluation, cohort study N= 204
Objective	To decrease the number of orders and total hospital spend for inpatient use of antineoplastic drugs of interest, while evaluating each case for urgent or emergent need for administration
Study Groups	Pre-implementation group (n= 131) Post-implementation group (n= 73)
Inclusion Criteria	Patients ≥ 18 years of age and received an antineoplastic agent restricted to the outpatient setting for an oncological indication
Exclusion Criteria	Patients who received a restricted agent for any indication other than cancer or if they were not officially admitted to the hospital
Methods	Patients were identified using a dispensing analysis report for the antineoplastic drugs of interest. Implementation of a criteria-for-use algorithm evaluating inpatient orders for urgent or emergent need, NCCN guideline recommendations, hospitalization status, and evidence supporting treatment continuation was evaluated by comparing inpatient use during the 3 years before (2013–2015) and after (2016–2018) implementation across five hospitals. Orders that did not meet the criteria were considered for outpatient administration.
Duration	January 1, 2013 to December 31, 2018
Outcome Measures	Primary: Total number of orders for restricted antineoplastic agents, hospital spending on these drugs Secondary: Median patient length of stay, incidence of patient mortality, documentation of improvement in patient symptoms, toxicities from treatment
Baseline Characteristics		Pre-implementation group (n= 131)	Post-implementation group (n= 73)
	Age, years (IQR)	65 (53–73)	59 (51–70)
	White	115 (87.7%)	59 (80.8%)
	Male	86 (65.6%)	38 (52.1%)
	Continuation versus new initiation Continuation New initiation	29 (22.1%) 102 (77.8%)	18 (24.7%) 55 (75.3%)
	Treatment documented as urgent or emergent	31 (23.7%)	30 (41%)
	Abbreviations: IQR, interquartile range.
Results		Pre-implementation (n= 185)	Post-implementation (n= 79)	p-value
	Total orders for restricted antineoplastic agents	185	79	N/A
	Immune therapy orders	0	4	N/A
	Hospital spend (average $/year)	522,456	199,336	0.0357
	LOS, days (IQR)	8 (5-16.5)	12 (8-20)	0.0049
	Overall mortality	13 (7.1%)	20 (24.7%)	<0.001
	Abbreviations: LOS, length of stay. Following implementation of the criteria-for-use algorithm, the number of restricted antineoplastic orders decreased from 319 to 141 (56%), and annual hospital spending decreased from $2,096,533 to $795,146 (62%). These reductions were largely driven by rituximab, with inpatient rituximab orders decreasing from 138 to 40 (71%), whereas use of the second most commonly prescribed restricted agent, bortezomib, changed minimally (17 vs 14 orders). Four immune therapy orders were approved after implementation compared with none before.
Adverse Events	Oxygen use (0 vs 6 patients; p= 0.001) and in-hospital mortality (6 vs 17 patients; p< 0.001) were higher after implementation, and no association was identified between cancer diagnosis and in-hospital death.
Study Author Conclusions	Implementation of a criteria-for-use algorithm was successful in limiting the use of select non-formulary antineoplastic agents in this study. Study outcomes suggest that a criteria-for-use algorithm is a systematic way to limit inappropriate use of any pharmacologic agent. This method was especially useful for high-cost antineoplastic agents, with a 62% decrease seen in annual hospital spending for these drugs in study outcomes.
Critique	The study describes an institutional criteria-for-use algorithm for restricting inpatient use of selected high-cost antineoplastic agents and demonstrated reductions in inpatient rituximab use and hospital spending. However, the algorithm was not specific to rituximab, and the publication provides limited detail regarding the approval process and how individual criteria were operationalized. Additionally, orders that were denied or deferred to the outpatient setting were not evaluated, limiting assessment of the algorithm's overall impact.

Table 1 References:
[2] Randle H, Smith LV, Padilla-Tolentino E, Goodgame BW. Evaluation of the use of non-formulary oncology medications restricted to outpatient use in hospitalized patients after implementation of a criteria-for-use algorithm. J Oncol Pharm Pract. 2020;26(4):882-890. doi:10.1177/1078155219877920

Inpatient Antineoplastic Medication Administration And Associated Drug Costs: Institution of a Hospital Policy Limiting Inpatient Administration
Design	Retrospective chart review N= 648
Objective	To evaluate the necessity and drug costs of administering antineoplastic medications in the inpatient setting and explore savings associated with the 2013 implementation of an institutional policy that defined criteria necessitating inpatient administration of antineoplastic medication
Study Groups	All patients (N= 648)
Inclusion Criteria	Patients 18 years of age and older receiving inpatient antineoplastic medications during January, April, July, and October of 2010, 2012, 2014, and 2015 at a community teaching hospital
Exclusion Criteria	Patients younger than 18 years of age and pregnant women
Methods	Retrospective chart review of patients receiving inpatient antineoplastic medications. Data collected included demographic information, diagnosis, reasons for hospital admission, antineoplastic regimen details, and drug costs. The necessity for inpatient administration was determined based on adherence to hospital policy. The institutional policy permitted inpatient antineoplastic administration for emergent chemotherapy, high-dose cisplatin (≥75 mg/m²), intra-arterial chemotherapy/chemoembolization/heated intraperitoneal chemotherapy, acute leukemia induction, ifosfamide, complex regimens requiring more than 6 hours of administration or observation, high-dose methotrexate (≥500 mg/m²), 23-hour observation, special circumstances approved by department chairs, and rituximab only when clinically necessary (e.g., emergency or monitoring required).
Duration	Data collection: January, April, July, and October of 2010, 2012, 2014, and 2015
Outcome Measures	Primary: Proportion of patients appropriately receiving antineoplastic medications in the inpatient setting Secondary: Comparison of drug costs of regimens meeting and not meeting policy criteria, trends in cancer diagnoses and drug regimens, comparison of rituximab use and cost
Baseline Characteristics		2010 (n= 179)	2012 (n= 206)	2014 (n= 123)	2015 (n= 140)
	Male	75 (42%)	79 (38%)	54 (44%)	57 (41%)
	Age, years (IQR)	60 (41–79)	59 (39–79)	58 (33–83)	61 (44–78)
	23-hour observation	50 (28%)	59 (29%)	19 (15%)	31 (22%)
	Abbreviations: IQR, interquartile range.
Results	A total of 648 patients received inpatient antineoplastic regimens. The proportion of regimens meeting institutional criteria for inpatient administration increased from 80% in 2010 and 78% in 2012 to 83% in 2014 and 91% in 2015 (p= 0.005), with significant differences between 2010 and 2015 (p= 0.003) and between 2012 and 2015 (p< 0.001). The annualized inpatient antineoplastic drug cost for regimens not meeting criteria decreased from $269,049 in 2010 to approximately $105,000 in 2014 and 2015, corresponding to an estimated annual cost savings of at least $163,602. Convenience-related inpatient chemotherapy administration decreased, and four exceptions to the institutional policy were approved after implementation. The policy restricted inpatient rituximab administration to clinically necessary situations, with outpatient administration preferred when feasible. Rituximab use differed across years (p= 0.049), although no pairwise differences remained after Bonferroni correction. Shifting appropriate inpatient rituximab administration to the outpatient setting was estimated to reduce annual inpatient drug costs by $111,004 to $234,548.
Adverse Events	Not applicable
Study Author Conclusions	Implementation of a policy establishing criteria for inpatient antineoplastic drug administration led to a decrease in both the number of patients receiving antineoplastic medications in the inpatient setting who did not meet the criteria and the associated drug costs. More education and implementation of further policies, specifically directed toward appropriate inpatient administration of rituximab, may increase the impact of this policy on the institution’s oncology medication costs. Further studies regarding the impact of maximizing administration of antineoplastics in the outpatient clinic setting on reimbursement are necessary to fully elucidate the drug–cost benefit of shifting antineoplastic medication administration to the outpatient clinic setting.
Critique	The study effectively demonstrates the impact of policy implementation on reducing inpatient antineoplastic drug costs and administration. However, the retrospective design and limited data collection periods may introduce selection bias and limit generalizability. The use of AWP instead of actual institutional costs may not fully reflect cost-saving potential. Further studies are needed to explore the impact of outpatient administration on reimbursement and cost savings.

Table 2 References:
[3] Foster AE, Reeves DJ. Inpatient Antineoplastic Medication Administration And Associated Drug Costs: Institution of a Hospital Policy Limiting Inpatient Administration. P T. 2017;42(6):388-393.

Retrospective review of non-formulary use of rituximab at the Alfred Hospital
Design	Retrospective review; conference abstract N= 15
Objective	To determine patterns of rituximab use, the reasons for non-formulary use and the appropriateness of rituximab prescribing at The Alfred.
Study Groups	All patients (N= 15)
Inclusion Criteria	Not reported in abstract
Exclusion Criteria	Not reported in abstract
Methods	Patients were identified through pharmacy records, and medical records were reviewed for patient demographics, indication, non-formulary approval details, prior and concomitant therapies, and treatment response. The appropriateness of rituximab prescribing was independently assessed by a senior hematologist not involved in the prescribing or approval process.
Duration	June 2000 to February 2005
Outcome Measures	Patterns of rituximab use; reasons for non-formulary use; appropriateness of prescribing; treatment response; rituximab expenditure; vial wastage
Baseline Characteristics	Not reported in abstract
Results	Rituximab prescribing was primarily from the Bone Marrow Transplant/Clinical Hematology Unit (86%), with indications including non-Hodgkin lymphoma in non-PBS-approved circumstances, post-transplant lymphoproliferative disease, and Glanzmann syndrome. Complete remission occurred in 6 patients (40%) and partial response in 2 patients (13%). Total rituximab expenditure was approximately $220,000, with approximately $5,600 in unavoidable vial wastage.
Adverse Events	Not assessed
Study Author Conclusions	In all cases, rituximab was only initiated when patients had failed alternative therapies. The non-formulary use of rituximab at The Alfred was considered clinically appropriate and the current non-formulary approval system should be continued.
InpharmD Researcher Critique	The abstract provides limited detail regarding the non-formulary approval process and does not describe the specific criteria used to approve inpatient rituximab use, although non-formulary approval was required.

Table 3 References:
[4] Radhakrishnan C. Retrospective review of non-formulary use of rituximab at the Alfred Hospital. Presented at: 27th Federal Conference of the Society of Hospital Pharmacists of Australia; November 2005. Accessed July 21, 2026. https://www.researchgate.net/publication/237053049_Retrospective_review_of_non-formulary_use_of_rituximab_at_the_Alfred_Hospital

Outcomes of Inpatient Administration of Restricted Antineoplastic Medications at a Large Academic Medical Institution
Design	Single-center retrospective chart review N= 23
Objective	To describe the use of formulary, outpatient-restricted oncology and hematology medications in the inpatient setting at a single-center, academic, and comprehensive cancer center
Study Groups	All patients (N= 23)
Inclusion Criteria	Adult patients (aged 18 years and older) who received at least one dose of a formulary, outpatient-restricted medication for an oncology or hematology condition in the inpatient setting
Exclusion Criteria	Patients who were pregnant, incarcerated, received a restricted medication as part of a clinical trial, administered a patient-supplied medication, acquired medication through a patient assistance program, or required admission for inpatient monitoring during medication administration
Methods	Retrospective chart review of patients who received at least one dose of a formulary, outpatient-restricted medication for oncology or hematology conditions. Under the institutional policy, requests for inpatient administration underwent an informal review involving the requesting prescriber, oncology pharmacist, and oncology P&T committee chair, with consideration of restriction status, insurance coverage, outpatient availability, and final approval by the oncology P&T chair.
Duration	January 1, 2015 to May 1, 2017
Outcome Measures	Primary: Percentage of formulary, outpatient-restricted medications continued to the outpatient setting Secondary: Overall survival, hospice enrollment, disease progression status, level of evidence supporting medication usage, cost
Baseline Characteristics		Patient Population (N= 23)
	Age, years (IQR)	59 (18–81)
	Male	18 (78.3%)
	White	15 (65.2%)
	Baseline ECOG Performance Score 0 1 2 3 4 N/A	1 (4.2%) 5 (20.9%) 7 (29.2%) 7 (29.2%) 2 (8.3%) 6 (25.0%)
	Renal Function GFR ≥ 60 GFR < 60	16 (66.7%) 8 (33.3%)
	Hepatic Function Normal Abnormal	20 (83.3%) 4 (16.7%)
	Clinical Status Deceased Alive Unknown	10 (43.5%) 6 (25.1%) 7 (30.4%)
	Abbreviations: ECOG, Eastern Cooperative Oncology Group; GFR, glomerular filtration rate.
Results	A total of 24 requests for formulary, outpatient-restricted medications were approved in 23 patients. Of the approved medications, 13 (54%) were continued in the outpatient setting after discharge, whereas 8 (33%) were not continued. Among medications not continued, 5 were discontinued due to patient death, 1 due to disease progression, 1 after transfer to another institution, and 1 patient was lost to follow-up.
Adverse Events	Not assessed
Study Author Conclusions	At UCSD, formulary, outpatient-restricted oncology and hematology medications were requested for patients with a poor ECOG performance status or who were near the end of life. Approximately one-third of the patients did not continue treatment with these medications to the outpatient setting. Based on the study results, we plan to incorporate an outpatient-restricted medication request form at our institution, and complete a post-implementation study with an expanded data set and collection timeframe. Having a formalized process for requesting formulary, outpatient-restricted oncology and hematology medications could optimize drug utilization in the inpatient setting.
Critique	The study evaluated outpatient-restricted oncology and hematology medications broadly and did not specifically assess rituximab. The single-center, retrospective design and small sample size limit the generalizability of the findings.

Table 4 References:
[5] Lau KM, Derry K, Dalton A, Martino J. Outcomes of Inpatient Administration of Restricted Antineoplastic Medications at a Large Academic Medical Institution. P T. 2019;44(8):481-496.