Staff Pharmacists Discuss Updated Carboplatin Drug Shortage Mitigation Strategies at the University of Illinois at Chicago Oncology Clinic Pharmacy

In March 2023, carboplatin joined the growing list of drug shortages within the United States. Carboplatin, a chemotherapy used alone or with other medications to treat many cancers, is manufactured by several companies including Accord and Pfizer; the manufacturers reported the shortages as being the result of production delays.¹

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Shortages of carboplatin present serious challenges for oncology practices. According to a Hematology/Oncology Pharmacy Association (HOPA) survey, oncology drug shortages led to interruptions in the timing of treatments, alterations in the dose or regimen administered, omission of doses when alternative agents were unavailable, complications in clinical research, and increased risk of medication errors and adverse outcomes.² Proper oversight, effective communication, and collaborative efforts between health care professionals, drug manufacturers, distribution centers, and government agencies are recommended to effectively manage chemotherapy drug shortages, placing what can become additional strain on an already taxed health system.³

A Case Study

The University of Illinois at Chicago (UIC) Oncology Clinic Pharmacy, part of the UI Health System, provides comprehensive services to the UIC Cancer Center’s oncology clinic patients. At the Oncology Clinic Pharmacy, inventory management strategies include creating and managing periodic automatic replenishment inventory levels of commonly utilized medications. Necessary drug inventory is identified based on expected patient treatments. When supply chain disruptions are anticipated, the usual practice is to increase stock levels to store approximately an extra week of product.

However, the total impact of the current carboplatin shortage on patient care in the Oncology Clinic Pharmacy remains difficult to quantify. For this reason, staff pharmacists at the Oncology Clinic Pharmacy have worked to better understand active mitigation and pharmaceutical sourcing strategies to better assess opportunities to improve care for patients with cancer in the UI Health System. From April 20, 2023, to June 20, 2023, there were 44 patients found to be on carboplatin regimens at the Oncology Clinic Pharmacy. Table 1 summarizes the distribution of these patients affected by current mitigation strategies during this period.

Current Mitigation Strategies⁴

Communicate Shortage With Health Care Providers and Staff

Communication regarding carboplatin shortage and updates were released to providers and staff at the UIC Cancer Center once manufacturers reported the occurrence of manufacturing delays.

Assess Current Inventory Daily

Pharmacy personnel performed physical inventory count of carboplatin daily.

Identify Inventory Needs

Staff pharmacists ran daily and weekly reports of patients scheduled to receive carboplatin and calculated expected patient doses based on patient specific factors: gender, height, weight, serum creatinine, age, and target area under the curve (AUC). The anticipated amount of carboplatin needed was compared with the on-hand carboplatin inventory to determine the day when our inventory of carboplatin would be insufficient for patients scheduled to receive treatment. This discrepancy was then communicated with providers and nursing personnel.

Prioritize Patients

Patients enrolled in clinical trials were prioritized, especially if the research protocol did not contain alternative options. Additionally, patients with curative treatment intent were prioritized over patients with palliative intent. If necessary, in patients with a palliative treatment goal, carboplatin was either omitted or treatment delayed until the pharmacy inventory was able to accommodate their doses.

Adjust Operational Workflow

If carboplatin was to be administered as part of a multichemotherapy regimen, the compounding of carboplatin was delayed until the administering nurse communicated with the pharmacy team that all previous chemotherapy in the treatment plan sequence was administered and well tolerated.

Alter Regimen Administered

On some occasions, providers opted to keep patients on schedule and omit doses of carboplatin from treatment regimens as opposed to delaying treatment start dates. For example, a provider decided to proceed with standard-of-care carboplatin plus pemetrexed with pembrolizumab for a patient with stage IV non–small cell lung cancer and treat the patient with pemetrexed and pembrolizumab alone on cycle 1 day 1.

For certain indications, another treatment option was to modify carboplatin to another platinum-based drug such as cisplatin or oxaliplatin. However, this modification required additional steps by clinic staff. Billing personnel obtained new insurance authorizations for these alternative drugs and associated supportive care medications, and patients were reconsented by providers. Additionally, treatment plans were modified to include pertinent laboratory parameters, including referrals for baseline auditory testing and urine output screening.

Alter Dose Administered

All carboplatin doses were rounded down to the nearest 10 mg, if such a change fell within a 10% variance of the original treatment plan dose. This procedure aligned with the institutional dose rounding protocol. In a few cases the carboplatin dose was significantly reduced (from AUC of 5 to AUC of 2) based on tolerance.

Adopt New Standardized Method of Carboplatin Dosing

In February 2023, the National Comprehensive Cancer Network (NCCN) provided an update on additional considerations when dosing carboplatin. Specifically, NCCN explained that using a minimum serum creatinine of 0.7 mg/mL helps to avoid overestimation of creatinine clearance in patients with abnormally low serum creatinine. Additionally, NCCN noted that it is beneficial to use an adjusted body weight in overweight or obese patients who have a body mass index of 25 kg/m² or greater. These additional considerations were implemented to provide more consistency, which also contributed to supporting the management of carboplatin inventory.

Intensify Procurement Process

Daily medication procurement typically occurs via the local distribution center of the primary pharmacy wholesaler. When supply shortages were identified, multiple strategies were utilized to procure backordered medication. These included the creation of itemized back-order lists, increased communication with respective wholesalers, and investigation of alternative options in the medication supply chain.

Constant communication was made with the drug distributor to increase drug allocation and request for medications to be shipped from alternative distribution centers. Local pharmaceutical drug representatives were also contacted to request emergency drop shipments.

Communication was attempted several times per week as estimated release dates and shipments from manufacturers were unpredictable. Emergency drop shipments were approved from 3 of 4 drug companies contacted. After emergency approvals were granted, drop shipments were placed by the primary wholesaler for delivery to the oncology pharmacy. This process required new lines of communication to be established between the pharmacy, the manufacturer, and the distributor.

Secondary wholesalers were also contacted to investigate the possibility of obtaining medications through a different supply chain, but a challenge encountered in this process was the inability to obtain drug allocation due to a lack of prior order history. Another obstacle to obtaining medications from third-party pharmacy wholesalers was an increase in drug cost.

Table 2 summarizes the difference in cost between wholesale acquisition cost and third-party wholesaler costs. To gain access to a standard priority list to obtain carboplatin, the cost was more than 8-fold higher than purchasing at wholesale acquisition cost. Access to a high priority list would represent a more than 900% increase from wholesale pricing.

Due to limited alternatives, dwindling institutional supply, and the need to procure carboplatin for potentially lifesaving treatments, the decision was made to proceed with ordering from third-party wholesalers. The approval process involved verification of track and trace processes of the wholesaler company and consultation with department leadership.

Chemotherapy drug shortages pose a serious threat to public health. Cooperation among manufacturers, wholesalers, and regulatory agencies will be needed to prevent critical shortages. However, strategies to curb excessive markup on essential medications remains necessary to protect access to care for patients, as this was a significant challenge faced by staff pharmacists in mitigating the impact of the carboplatin drug shortage on patients within the UI Health System.

Oncology pharmacists continue to play vital roles on the health care team when overcoming challenging drug shortages of crucial oncology medications, such as those facing the Oncology Clinic Pharmacy and their patients. The impact of these mitigation strategies on patient care remains difficult to quantify but important to discuss and assess to better understand improvements that can be made to current strategies.

References

1. Current drug shortages: carboplatin solution for injection. American Society of Health-System Pharmacists. Updated July 11, 2023. Accessed April 4, 2023. https://www.ashp.org/drug-shortages/current-shortages

2. McBride A, Hudson-DiSalle S, Pilz J, et al. National survey on the effect of oncology drug shortages in clinical practice: a Hematology/Oncology Pharmacy Association survey. JCO Oncol Pract. 2022;18(8):e1289-e1296. doi:10.1200/OP.21.00883

3. Drug shortages issue brief. Hematology/Oncology Pharmacy Association. Updated January 19, 2022. Accessed April 18, 2023. https://www.hoparx.org/documents/64/HOPA_Drug_Shortages_Issue_Brief_-_Updated_01.19.22_FINAL_1.pdf

4. ASHP guidelines on managing drug product shortages. American Society of Health-System Pharmacists. Accessed April 18, 2023. https://www.ashp.org/-/media/assets/policy-guidelines/docs/guidelines/managing-drug-product-shortages.ashx

About the Authors

Irene Ryu, PharmD, CAPM; Haleh Maali, PharmD, BCPS; and Anna Xie, PharmD, BCPS, BCOP, hold positions as clinical staff pharmacists at the University of Illinois at Chicago Oncology Clinic Pharmacy and clinical instructors of pharmacy practice at the University of Illinois at Chicago College of Pharmacy.

Daniel Anzalone, PharmD, holds a position as an assistant director in ambulatory care pharmacy at the University of Illinois Health System and clinical instructor of pharmacy practice at the University of Illinois at Chicago College