Drug Criteria & Outcomes: Pegfilgrastim formulary evaluation

By Jeremy Vandiver, PharmD Candidate
Auburn University, Auburn, AL

Colony-stimulating factors

  • Sargramostim (Leukine)
  • Filgrastim (Neupogen)
  • Pegfilgrastim (Neulasta)

Mechanism of action

Similar to filgrastim and sargramostim, pegfilgrastim stimulates neutrophil proliferation, differentiation, maturation, and activation by acting on specific receptors on progenitor cells. It also stimulates their migration and cytotoxicity. Currently, it is indicated only to lower the risk of infection in patients undergoing chemotherapy regimens known to cause febrile neutropenia. This condition is clinically important because duration of neutropenia has been directly correlated with risk of infection.

While filgrastim and pegfilgrastim act primarily on neutrophils, sargramostim also acts on eosinophils and monocytes to increase their proliferation and activity.

Pegfilgrastim and filgrastim are both produced by inserting a human G-CSF gene into Escherichia coli via a plasmid. In the case of pegfilgrastim, a polyethylene glycol molecule then is added to the filgrastim molecule at the N-terminal methionyl residue.

Sargramostim is produced using recombinant DNA technology in yeast.

Dosing

Pegfilgrastim is given once per chemotherapy cycle as a subcutaneous (SC) 6 mg injection one day after the cytotoxic chemotherapy regimen.

Pegfilgrastim currently is not approved for use in infants or children. It also is not approved for adolescents weighing less than 45 kg. For patients meeting these criteria, 6 mg once per chemotherapy cycle should be administered subcutaneously.

Filgrastim is dosed as a 5 mcg/kg/d SC or intravenous (IV) infusion beginning 24-72 hours after the chemotherapy regimen and continuing for 7-14 days or until absolute neutrophil counts (ANC) reach 10,000/uL.

Sargramostim is dosed 250 mcg/m2/d SC or IV infusion 24-72 hours after chemotherapy regimen completion continuing until ANC reaches 10,000/uL.

Pharmacokinetics

The kinetics of pegfilgrastim are interesting: Clearance decreases as the dose is escalated. This is because elimination of the drug is directly dependent on neutrophil numbers. As neutrophil numbers increase, so does the elimination of the drug. For more information on pharmacokinetics, see Table 1.

Monitoring parameters

Pegfilgrastim: Complete blood count (CBC) and platelet count should be taken before beginning chemotherapy. After initiation, platelets and hematocrit should be monitored regularly.

Filgrastim: CBC and platelets should be obtained prior to chemotherapy, then twice per week during therapy. White blood counts (WBC) should be monitored regularly, especially during the expected rise following chemotherapy-induced nadir.

Sargramostim: CBC is recommended twice per week during therapy. Renal and hepatic function should be evaluated every two weeks during therapy in patients with a prior history of dysfunction. Body weight and hydration status also should be monitored.

Indications

Pegfilgrastim currently is indicated only for chemotherapy-induced neutropenia.

Filgrastim currently is indicated for the following:

  • Treatment of severe chronic congenital neutropenia, chronic cyclic neutropenia, and idiopathic neutropenia.
  • Treatment of patients with neutropenia due to HIV or its treatment, or to prevent infectious complications.
  • Treatment of myelodysplastic syndrome.
  • Primary or secondary prophylaxis for patients on chemotherapeutic regimens with a 40% or higher incidence of febrile neutropenia.
  • Primary prophylaxis for febrile neutropenia or to speed neutrophil recovery time for patients with acute lymphoid leukemia.
  • Peripheral blood stem cell mobilization prior to and during leukapheresis for patients undergoing bone marrow ablation.
  • Decreasing febrile and non-febrile neutropenia for bone marrow transplant patients.
  • Decreasing length of neutropenia following reinfusion of peripheral blood stem cells.
  • Treatment of aplastic anemia.

Sargramostim currently is indicated for the following:

  • Treatment of patients with neutropenia due to HIV or its treatment, or to prevent infectious complications.
  • Treatment of myelodysplastic syndrome.
  • For myeloid recovery following bone marrow transplantation.
  • Decreasing length of neutropenia following reinfusion of peripheral blood stem cells.
  • Peripheral blood stem cell mobilization prior to and during leukapheresis for patients undergoing bone marrow ablation.
  • Prevention of chemotherapy-induced neutropenia and decreasing the incidence of febrile neutropenia in patients receiving myelosuppressive therapy.
  • Treatment of acute myelogenous leukemia for patients age 55 and older.
  • Treatment of aplastic anemia.
  • Adjuvant treatment of malignant melanoma following surgery for Stage III or IV melanoma in patients who are at high risk for recurrence.
  • Treatment of HIV infection.

Contraindications/warnings

  • Pegfilgrastim should not be used in patients who are allergic to pegfilgrastim, filgrastim, E. coli-derived proteins, or any component of the formulation.
  • Pegfilgrastim should not be used concomitantly with chemotherapy, radiation, or myelosuppressive therapy.
  • Pegfilgrastim should not be used 14 days before or within 24 hours following cytotoxic chemotherapy.
  • Pegfilgrastim can act as a growth factor for any tumor type.
  • Pegfilgrastim should be used cautiously in patients with myeloid malignancies.
  • Allergic-type reactions have occurred in patients receiving pegfilgrastim’s parent compound.
  • Splenic rupture and adult respiratory distress syndrome have been reported in rare cases.
  • Sickle cell crisis has been reported following pegfilgrastim administration.
  • Pegfilgrastim is not approved for use in pediatric patients.
  • Pegfilgrastim is not approved for use in adolescents weighing less than 45 kg.

Adverse drug reactions

Other adverse effects included nausea, fatigue, alopecia, diarrhea, vomiting, constipation, fever, anorexia, skeletal pain, headache, taste perversion, dyspepsia, myalgia, insomnia, abdominal pain, arthralgia, generalized weakness, peripheral edema, dizziness, granulocytopenia, stomatitis, mucositis, and neutropenic fever. However, it is difficult to determine whether these were attributable to the drug, chemotherapy, or underlying disease.

Serious reactions that should also be considered included splenic rupture, adult respiratory distress syndrome, sickle cell disease crisis, and allergic reactions. Warnings of these reactions are primarily due to the experience with pegfilgrastim’s parent compound.

As with any newly released drug, there is limited clinical experience, and unknown adverse drug reactions may surface as it is used in complex clinical situations not evaluated in clinical trials.

Pegfilgrastim and filgrastim should be avoided by those with a hypersensitivity to E. coli-derived preparations.

Those with a hypersensitivity to yeast should avoid sargramostim.

Adverse drug reaction information is summarized in Table 2.

Drug interactions

Formal drug interaction studies are not yet available for pegfilgrastim. However, it is expected that, as with the other colony-stimulating factors, drugs that potentiate neutrophil release may have some interaction (i.e., lithium and corticosteroids).

Pegfilgrastim also should not be given 14 days before a cytotoxic chemotherapy agent or within 24 hours of administering a cytotoxic chemotherapy agent. This is due to pegfilgrastim’s stimulatory effect that causes rapid proliferation of cells, and the cytotoxic agent actively targeting rapidly proliferating cell lines.

Clinical studies

Study No. 1: Holmes FA, et al. Blinded, randomized, multicenter study to evaluate single-administration pegfilgrastim once per cycle versus daily filgrastim as an adjunct to chemotherapy in patients with high-risk Stage II or Stage III/IV breast cancer. J Clin Oncol 2002;20:727-731.

Objective: To evaluate whether pegfilgrastim (100 mcg/chemotherapy cycle) is as safe and effective as daily filgrastim (5 mcg/kg/d) in reducing chemotherapy-induced neutropenia.

Study design/patient population: Blinded, randomized, multicenter trial involving 310 patients. Patients were stratified with regard to sex, age, race, prior chemotherapy and prior radiotherapy, disease stage, and baseline ANC.

Inclusion criteria:

  • Men or women age 18 and older diagnosed with high-risk Stage II or III/IV breast cancer.
  • Patients had to be chemotherapy-naïve or have completed no more than one regimen of chemotherapy; previous regimen must have been completed more than four weeks before randomization.
  • ANC greater than 1.5 X 109 cells/L; platelet count greater than 100 X 109 cells/L.
  • Adequate hepatic and renal function.

Exclusion criteria:

  • Patients currently enrolled in investigational studies or who had been enrolled in studies in the past 30 days.
  • Prior exposure to pegfilgrastim; prior bone marrow or stem-cell transplantation.
  • Pregnant or breast-feeding.
  • Had received antibiotics within 72 hours of chemotherapy.
  • Had radiation therapy in the past four weeks.
  • Lifetime total cumulative dose greater than 240 mg/m2 of doxorubicin or more than 600 mg/ m2 of epirubicin.

Endpoints: The primary efficacy endpoint was duration of grade 4 neutropenia in cycle 1 (see Table 3 for information on duration of grade 4 neutropenia). Other efficacy endpoints included duration of grade 4 neutropenia in cycles 2-4, depth of ANC nadir in each cycle, rate of febrile neutropenia, and time to ANC recovery in each cycle. Safety endpoints included incidence of adverse events, changes in lab values, and presence of antibodies.

Treatment regimens: Patients received either pegfilgrastim 100 mcg/kg SC or filgrastim 5 mcg/ kg/d SC 24 hours after each chemotherapy cycle. Patients in the pegfilgrastim group received placebo injections to remain blinded. Both groups received doxorubicin (60 mg/m2) followed one hour later by docetaxel (75 mg/ m2). Chemotherapy was repeated every three weeks for up to four cycles.

Results:

  • Depth of ANC nadir: Pegfilgrastim achieved a 1.132:1 ratio of higher nadir over filgrastim.
  • Rate of febrile neutropenia: Febrile neutropenia occurred in 9% of the pegfilgrastim group vs. 18% of the filgrastim group (P = 0.029).
  • Time to ANC recovery: Pegfilgrastim was favored by 0.4 days (9.3 vs. 9.7).
  • Adverse drug reaction occurrences were very similar in the two groups.
  • Both groups had mild, transient increases in LDH, AST, and ALT.
  • No neutralizing antibodies were detected in either group.

Conclusion: The authors concluded that pegfilgrastim is as safe and effective as filgrastim in decreasing chemotherapy-induced neutropenia.

Limitations:

  • Small sample size.
  • Statistical methods were not described.
  • P values were not reported in some instances.
  • Trial was supported by Amgen, the manufacturer of pegfilgrastim.

Strengths:

  • Study objective is clearly stated.
  • Study endpoints were clearly defined.
  • Intent-to-treat analysis was performed.
  • Patients were closely matched with regard to sex, age, race, prior chemotherapy or radiotherapy, disease stage, and baseline ANC.

Study No. 2: Johnston E, et al. Randomized, dose-escalation study of SD/01 compared with daily filgrastim in patients receiving chemotherapy. J Clin Oncol 2000;18:2522-2528.

Objective: To evaluate the safety, clinical response, and pharmacokinetics of pegfilgrastim compared with filgrastim in patients with non-small cell lung cancer (NSCLC).

Study design/patient population: Randomized, open-label, single-center, dose-escalation trial involving 13 patients.

Inclusion criteria:

  • Men and women age 18 and older who had a diagnosis of NSCLC.
  • ANCs greater than 1.5 X 109 cells/L, platelet counts greater than 100 X 109 cells/L, and hemoglobin of at least 9 g/dL.
  • Patients had to have adequate renal and hepatic function.

Exclusion criteria:

  • Previous systemic chemotherapy or extensive radiotherapy.
  • Current uncontrolled infection.
  • Cancer other than NSCLC that was not in remission.
  • Known HIV infection.
  • Sensitivity to E. coli-derived products.
  • Women could not be breast-feeding and had to take adequate measures to avoid becoming pregnant.

Treatment regimens: Patients were randomized in a 3:1 ratio to receive 30, 100, or 300 mcg/kg/d of pegfilgrastim or 5 mcg/kg/d of filgrastim. The study was divided into two cycles, a 14-day prechemotherapy cycle and a 21-day postchemotherapy cycle. Pegfilgrastim patients received one dose in each cycle. Filgrastim patients received daily doses for five days in cycle 0 and then daily injections 24 hours following chemotherapy in cycle 1. Carboplatin (given to area under the curve of six) and paclitaxel 225 mg/m2 were given on day 1 and 2, respectively, to both groups in cycle 1.

Monitoring techniques: In cycle 0, daily CBCs were performed, and chemistry panels were drawn on days 1, 8, and 15. CD 34+ cells were assayed daily. In cycle 1, chemistry panels were performed on days 1, 8, and 15. Antibody testing was done on days 1 and 22, and CD 34+ cell counts were performed daily. In each cycle, samples for pharmacokinetic analysis were obtained several times during the first 48 hours and then daily. Patients were interviewed daily by telephone and examined once weekly. Adverse events were reported with investigators determining severity and causality.

Results:

  • Both groups had a rapid ANC increase upon initiation; however, the duration of this response was more sustained in the pegfilgrastim regimens.
  • Duration of ANC response and peak ANC response were dose-dependent in the pegfilgrastim groups.
  • CD 34+ count of pegfilgrastim at 30 mcg/ kg/d was similar to filgrastim.
  • Clearance of pegfilgrastim was observed to decrease with increasing dose, but increased as ANC returned to normal levels.
  • Lab values showed all groups experiencing an almost identical decrease in platelets. All groups also experienced mild, transient increases in LDH, ALP, and uric acid.
  • The only adverse event directly correlated with pegfilgrastim was mild-to-moderate bone pain.
  • Seroreactivity occurred in four of 19 samples taken in the pegfilgrastim group; however, no neutralizing antibodies were discovered.

Conclusion: The authors concluded that a single dose of pegfilgrastim allows adequate drug concentration without developing toxicity. They also concluded that pegfilgrastim was therapeutically equivalent to filgrastim.

Limitations:

  • Very small sample size.
  • Open-label design increases the risk of bias.
  • Patient stratification data were not shown.
  • Endpoints were not defined.
  • Statistical tests were not described.
  • Study was supported by Amgen.

Study No. 3: Green M, et al. A randomized, double-blinded Phase III study evaluating fixed-dose, once-per-cycle pegylated filgrastim (SD/01) vs. daily filgrastim to support chemotherapy for breast cancer. Proc Amer Soc Clin Oncol; 2001. Abstract available at: www.asco.org/prof/me/ html/01abstracts/0009/90.htm. Accessed June 10, 2002.

Study objective: To compare fixed-dose, once-per-cycle pegylated filgrastim to daily filgrastim to provide support to patients receiving chemotherapy.

Study design: Randomized, double-blinded Phase III study.

Patients and procedures: One hundred fifty-seven patients being treated with doxorubicin and docetaxel at 35 centers were randomized to receive either SD/01 6 mg SC or filgrastim 5 mcg/kg/d one day after chemotherapy, then placebo or 5 mcg/kg/d filgrastim until ANC was greater than 10 X 109 cells/L or for 14 days, whichever came first.

Results:

  • Sixty-eight SD/01 and 62 filgrastim patients with similar incidences of severe neutropenia (82% vs. 84%) were evaluated.
  • The mean duration of severe neutropenia differed by less than 0.2 days; SD/01 was slightly favored.
  • Severe neutropenia incidence was 13% vs. 20%, also slightly favoring SD/01.
  • Adverse events were comparable, including an assessment of bone pain.

Conclusion: A single fixed dose of SD/01 at 6 mg was comparable to multiple daily injections of filgrastim at 5 mcg/kg/d in providing ANC support. The authors believed this could lead to simplified management in chemotherapy patients.

Limitations:

  • Only abstract is available.
  • All patients not accounted for and evaluated.
  • Actual numbers were not provided, only percentages.
  • Confidence intervals and P values were not included.
  • Only reported information evaluated in chemotherapy cycle 1.
  • Specific adverse events and incidences were not reported.
  • Relatively small number of patients.

Study No. 4: Holmes FA, et al. A single dose of pegfilgrastim is as effective as daily filgrastim to reduce the duration of severe, chemotherapy-induced neutropenia. Proc Amer Soc Clin Oncol; 2000. Abstract available at: www.asco.org/prof/me/html/00abstracts/bmt/m_191.htm. Accessed June 10, 2002.

Study objective: To determine if a single dose of pegfilgrastim is as effective as daily filgrastim to reduce the duration of severe, chemotherapy-induced neutropenia.

Study design: Randomized, double-blinded with additional cohorts.

Patients and procedures: One hundred fifty-two Stage II-IV breast cancer patients were treated with doxorubicin (60 mg/m2) and docetaxel (75 mg/m2) followed with either pegfilgrastim (100 mcg/kg) or filgrastim (5 mcg/kg/d), repeated every 21 days for four cycles. Additional patients were randomized to receive open-label 30, 60, or 100 mcg/kg doses of pegfilgrastim.

Endpoints: The primary endpoint was duration of severe neutropenia in cycle 1 (ANC < 500 cells/L). Additional endpoints included:

  • The duration of severe neutropenia in cycles 2-4.
  • ANC profile, including time to ANC recovery.
  • Pharmacokinetics in cycle 1.
  • Safety profile in cycles 1-4.

Results:

  • Patients treated with 30 or 60 mcg/kg of pegfilgrastim were at an increased risk of inadequate neutrophil recovery.
  • Pegfilgrastim displayed non-linear kinetics with a mean half-life of approximately 80 hours compared to five hours for filgrastim.
  • The safety profile of pegfilgrastim was similar to filgrastim.
  • No antibody formation to either agent was observed.
  • Pegfilgrastim dosed 100 mcg/kg once per cycle required fewer injections, yet resulted in the same duration as filgrastim daily.

Conclusion: Pegfilgrastim administered once per chemotherapy cycle is as effective as filgrastim administered daily.

Limitations:

  • Only abstract available.
  • No actual numbers, percentages, confidence intervals, or P values were reported.
  • Study included blinded and unblinded patients.
  • Inclusion and exclusion criteria were not stated.
  • Conclusion of authors was reported without reporting information analyzed to reach these conclusions.
  • Open-label study is prone to bias.

Study No. 5: Vose MD, et al. Single-dose pegfilgrastim (SD/01) is as effective as daily filgrastim following ESHAP chemotherapy for subjects with non-Hodgkin’s lymphoma or Hodgkin’s disease: Results of a randomized, open-label study. Blood 2001;98:799a.

Study objective: To compare the safety and efficacy of a single dose of pegfilgrastim (100 mcg/kg) with daily doses of filgrastim (5 mcg/kg/d) in 60 subjects with relapsed or refractory non-Hodgkin’s lymphoma (NHL) or Hodgkin’s disease (HD) receiving ESHAP (etoposide, methylprednisolone, cisplatin, and cytarabine) chemotherapy.

Study design: Randomized, open-label trial.

Patients and procedures: Pegfilgrastim patients received a single SC injection per chemotherapy cycle. Filgrastim patients received daily SC injections for 12 days or until ANC was greater than 10 X 109 cells/L, whichever occurred first. The primary endpoint was the duration of grade 4 neutropenia (ANC less than 500 cells/L).

Results:

  • The incidence of grade 4 neutropenia was 68% for filgrastim and 69% for pegfilgrastim.
  • Mean duration of severe neutropenia was 2.4 days for filgrastim and 2.8 days for pegfilgrastim.
  • Incidence of febrile neutropenia in cycles 1 and 2 was 19% for filgrastim and 21% for pegfilgrastim (ANC less than 500 cells/L with fever higher than 38.2° C).
  • The median time for ANC recovery in cycle 1 was 15 days for filgrastim and 16 days for pegfilgrastim (ANC greater than 2,000 cells/L).
  • No differences were noted in incidence, duration, severity of bone pain, or other adverse events between groups.

Conclusion: A single SC injection of pegfilgrastim provided neutrophil support with safety and efficacy profiles that were similar to those provided by daily SC injections of filgrastim in subjects with NHL or HD receiving ESHAP chemotherapy. The once-per-cycle dosing regimen of pegfilgrastim simplifies the management of neutropenia and may improve patient quality of life.

Limitations:

  • Only abstract available.
  • Small study population.
  • Open-label design increases risk of bias.
  • No actual numbers, confidence intervals, or P values were reported.
  • Inclusion and exclusion criteria were not described.

Study No. 6: Crawford J, et al. A Phase II multicycle trial of pegfilgrastim compared to filgrastim after myelosuppressive chemotherapy. International Association for the Study of Lung Cancer. World Conference on Lung Cancer. Tokyo; September 2000.

Study objective: To evaluate the pharmacodynamic and safety profile of a single dose of SD/01 in multicycle chemotherapy.

Study design: Phase II, randomized trial.

Patients and procedures: Eighty patients were randomized to receive 30, 60, or 100 mcg/kg of pegfilgrastim as a single injection or filgrastim 5 mcg/kg/d until adequate ANC was achieved (ANC greater than 10 X 109 cells/L).

Results:

  • Mean duration of ANC less than 500 cells/L was one day (range 0-4).
  • No differences were seen with thrombocytopenia or anemia in each cycle.
  • Safety profile was very similar between the groups.
  • SD/01 developed no dose-limiting toxicity.
  • No antibodies developed; however, some seroreactivity was noted.
  • SD/01 100 mcg/kg demonstrated greater improvement in neutropenia during later cycles and moved on to a Phase III trial.

Conclusion: SD/01 as a single dose 24 hours following chemotherapy appears comparable to daily filgrastim multiple doses.

Limitations:

  • Only abstract available.
  • Small sample size.
  • No confidence intervals or P values are reported.
  • Numbers are not given to evaluate some of the authors’ conclusions.
  • Very limited information reported.

Study No. 7: George TK, et al. Pharmacokinetic profiles of fixed-dose single pegfilgrastim administration in patients with non-Hodgkin’s lymphoma. Blood 2001;98:27b.

Study objective: To characterize the pharmacokinetics of pegfilgrastim and ANC responses after administration of fixed-dose pegfilgrastim in newly diagnosed non-Hodgkin’s lymphoma patients receiving CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy.

Study design: Open-label, multicenter trial.

Patients and procedures: Patients were treated with a single 6 mg injection of pegfilgrastim approximately 24 hours following chemotherapy. Pharmacokinetics, duration of grade IV neutropenia, time to ANC recovery, safety profile, and incidence of febrile neutropenia were measured.

Results:

  • Maximal concentration of pegfilgrastim occurred 24 hours after dosing.
  • ANC had recovered by day 11, and serum concentration of pegfilgrastim was 0.93 ng/mL.
  • Serum levels of pegfilgrastim declined as ANC returned to normal, demonstrating a neutrophil-mediated, self-regulating clearance.
  • Median terminal half-life was 42 hours.
  • Grade IV neutropenia occurred in 43% (95% confidence interval [CI]) of patients with a mean duration of 1 ± 1.4 days.
  • Median time to ANC recovery was 10 days (ANC greater than 1,000 cells/L).
  • Febrile neutropenia occurred in 11% (95% CI) of patients (ANC less than 500 cells/L with temperature of 38.2° C).
  • Body weight had no effect on duration of grade 4 neutropenia.
  • Duration of severe neutropenia was longer in patients older than age 65 and in patients with bone marrow involvement; febrile neutropenia also occurred at an increased rate. Study stated that neither was statistically significant.
  • Mild-to-moderate bone pain occurred in some patients.
  • Baseline and therapy lab values were similar.

Conclusion: The authors concluded that in non-Hodgkin’s lymphoma patients treated with CHOP, a single 6 mg injection of pegfilgrastim provided adequate drug exposure for neutrophil support regardless of body weight.

Limitations:

  • Only abstract available.
  • Small sample size.
  • No P values were given to assess statistical significance.
  • Not all numbers reported for each endpoint.

Evaluation of literature

Few full-text articles are currently available to evaluate the use of pegfilgrastim. The first study in this evaluation provides enough information to adequately evaluate it and possibly apply its results. However, the other available full-text study lacks a sufficient sample size for its results to be applicable to a population. The remaining evaluations are abstracts of clinical trials. Although these do trend toward the results found in the full-text articles, abstracts do not provide enough complete data to make a decision regarding therapy.

Cost

The cost figures below assume 10 days of therapy for filgrastim and sargramostim because the literature estimates ranged from six to 11 days of required therapy for ANC levels to rise to the required range. It also assumes pegfilgrastim would act equivalently to 10 days of daily injections of filgrastim and sargramostim. Weight figures assume ideal body weight of six-foot male. Values were calculated to give an estimate of the average cost per chemotherapy cycle of each drug.

Huntsville (AL) Hospital spent approximately $340,000 on colony-stimulating factors during the last year. If the assumptions used in calculating the average cost per chemotherapy cycle were carried over and pegfilgrastim were to be utilized in 30% of the annual usage, cost would increase by approximately $56,000.

Storage

Pegfilgrastim should be stored in a refrigerator (2-8° C). It should not be frozen. It may be kept at room temperature for 48 hours. It should be protected from light.

Pegfilgrastim should be allowed to reach room temperature prior to injection. If accidentally frozen, allow to thaw in refrigerator. If frozen more than once, discard.

Ways to decrease potential medication errors with colony-stimulating factors

Because each of these colony-stimulating factors has a unique dosing regimen, there is an increased possibility of medication errors. Some of these errors may be avoided by the following measures:

  • conducting multidisciplinary education programs;
  • educating about differences between dosing of colony-stimulating factors;
  • stressing that pegfilgrastim is a once-per-chemotherapy-cycle dose instead of daily;
  • stressing that pegfilgrastim should only be administered SC; whereas the others can be administered SC or by IV infusion;
  • stressing that pegfilgrastim is formulated in milligrams, whereas the others are in micrograms;
  • stressing the fact that pegfilgrastim should not be diluted, as the other two colony-stimulating factors are.

Conclusion and recommendation

Based on the currently available literature, pegfilgrastim appears to be very similar to filgrastim and sargramostim in safety and efficacy. With safety and efficacy being similar, cost becomes a consideration with formulary evaluation. While use in the outpatient setting could decrease hospital use and overall cost, this is an unpredictable situation that cannot be accurately described. As illustrated in the previous cost section, addition to the formulary would cause a considerable increase in the cost of treating individual patients within the hospital with colony-stimulating factor therapy. Also, inventory cost would have to be considered, as well as the possibility of increased medication errors due to the different dosing regimens of each of the colony-stimulating factors. Based on these aspects, it is currently recommended that pegfilgrastim be assessed non-formulary status and not be routinely stocked.

References

Filgrastim. Drug Facts and Comparisons. St. Louis: Facts and Comparisons; 2001:139-41.

"Filgrastim." In: McEvoy GK, ed. AHFS 2002: Drug Information. Bethesda, MD: American Society of Health System Pharmacists; 2002:1502-1510.

Filgrastim (monograph in electronic version). MICROMEDEX Healthcare Series. Englewood, CO: MICROMEDEX; 2001.

Filgrastim. Physicians’ Desk Reference. 55th ed. Montvale, NJ: Medical Economics Co.; 2001:551-556.

Personal communication. Cindy Hall, pharmacy buyer, Huntsville (AL) Hospital System Pharmacy. May 2002.

"Sargramostim." In: McEvoy GK, ed. AHFS 2002: Drug Information. Bethesda, MD: American Society of Health System Pharmacists; 2002:1511-1520.

Sargramostim. Drug Facts and Comparisons. St. Louis: Facts and Comparisons; 2001:141-144.

Sargramostim (monograph in electronic version). MICROMEDEX Healthcare Series. Englewood, CO: MICROMEDEX; 2001.

Sargramostim. Physicians’ Desk Reference. 55th ed. Montvale, NJ: Medical Economics Co.; 2001:1554-1558.