|
Filgrastim (Neupogen)
and Pegfilgrastim (Neulasta) are Recombinant Granulocyte Colony Stimulating
Factors (G-CSF) that acts on hematopoietic cells by binding to specific
cell surface receptors thereby stimulating proliferation, differentiation,
commitment, and end cell functional activation. They are a growth factor
that primarily stimulates neutrophils and neutrophil precursors.
Neulasta is a longer acting form of Neupogen. It is a covalent conjugate of
Neupogen with monomethoxypolyethylene glycol that allows the prolonged
persistence of Neulasta in vivo. The half-life of Neulasta ranged from
15-80 hours after SC injection and Neupogen’s is approximately 3.5 hours.
This policy recommends against the routine use of Neupogen and Neulasta in
uncomplicated cases of fever and neutropenia. Therapy with Neupogen and
Neulasta is recommended in conditions in which worsening of the course is
predicted, there is an expected long delay in recovery of the marrow,
patients remain severely neutropenic and have documented infections that do
not respond to appropriate antimicrobial therapy.
This policy applies to both existing G-CSF agents as well as future agents
of their class, which will be further restricted by any applicable FDA
limitations to their coverage.
Indications:
Neupogen will be considered reasonable and
necessary for the following specific indications:
1. Cancer Patients Receiving Myelosuppressive Chemotherapy
Neupogen is indicated to decrease the incidence of infection, manifested by
febrile neutropenia, in patients with non-myeloid malignancies receiving
myelosuppressive anti-cancer drugs associated with a clinically significant
incidence of febrile neutropenia. American Society for Clinical Oncology
guidelines (ASCO) remain the de facto standard of care unless specifically
superceeded.
Link to ASCO:
2006 Update of Recommendations for the Use of White Blood Cell Growth
Factors: An Evidence-Based Clinical Practice Guideline
The recommended starting dose of Neupogen is 5 µg/kg/day, administered as a
single daily SC bolus injection, by short IV infusion (15-30 minutes), or
by continuous SC or continuous IV infusion. Doses may be increased in
increments of 5 µg/kg for each chemotherapy cycle, according to the
duration and severity of the Absolute Neutrophil Count (ANC) nadir.
Neupogen is administered daily for up to 2 weeks, until the ANC has reached
10,000/mm 3. Neupogen therapy should typically be discontinued
if the ANC surpasses 10,000/mm 3 and/or the patient becomes
afebrile, or the patient has received the drug for a maximum of 14 days per
treatment regimen.
CBC and platelet count should be obtained prior to chemotherapy, and at
regular intervals (twice per week) during Neupogen therapy.
2. Acute Myeloid Leukemia Receiving Induction or Consolidation
Chemotherapy
Neupogen is indicated for reducing the time to neutrophil recovery and the
duration of fever following induction or consolidation chemotherapy
treatment of adults with AML.
Recommended starting dose is 5mcg/kg/day SC until: ANC 1,000 cells/mm for 3
days or ANC >10,000 cells/mm for 1 day for a maximum of 35 days.
3. Cancer Patients Receiving Bone Marrow Transplant (BMT)
Neupogen is indicated to reduce the duration of neutropenia and
neutropenia-related clinical sequelae (e.g. febrile neutropenia, in
patients with non-myeloid malignancies undergoing myeloablative
chemotherapy followed by marrow transplantation)
The recommended dose of Neupogen following BMT is 10 µg/kg/day given as an
IV infusion of 4 or 24 hours, or as a continuous 24 hour SC infusion. For
patients receiving BMT, the first dose of Neupogen should be administered
at least 24 hours after cytotoxic chemotherapy and at least 24 hours after
bone marrow infusion.
During the period of neutrophil recovery, the daily dose of Neupogen should
be titrated against the neutrophil response as follows:
|
Absolute
Neutrophil Count
|
Neupogen Dose
Adjustment
|
|
When ANC >
1000/mm 3 for 3 consecutive days
|
Reduce to 5
µg/kg/day*
|
|
then:
|
|
|
If ANC remains > 1000/mm
3for 3 more consecutive days
|
Discontinue Neupogen
|
|
then:
|
|
|
If ANC decreases to
<1000/mm 3
|
Resume at 5
µg/kg/day
|
* If ANC decreases to <1000/mm 3at any time during the 5
µg/kg/day administration, Neupogen should be increased to 10 µg/kg/day, and
the above steps should then be followed.
Frequent CBCs and platelet counts are recommended (at least three times per
week) following marrow transplantation.
4. Patients Undergoing Peripheral Blood Progenitor Cell (PBPC)
collection and therapy
Neupogen is indicated for the mobilization of hematopoietic progenitor
cells into the peripheral blood for collection by leukapheresis.
The recommended dose of Neupogen for the mobilization of PBPC is 10
µg/kg/day subcutaneously, either as a bolus or a continuous infusion. It is
recommended that Neupogen be given for at least 4 days before the first
leukapheresis procedure and continued until the last leukapheresis.
Neupogen dose-modification should be considered for those patients who
develop a WBC count >100,000/mm.
Neutrophil counts should be monitored after 4 days of Neupogen.
5. Patients With Severe Chronic Neutropenia (ANC less than 500/mm)
Neupogen in indicated for chronic administration to reduce the incidence
and duration of sequelae of neutropenia (e.g. fever, infections,
oropharyngeal ulcers) in symptomatic patients who has been confirmed
definitively with a diagnosis of congenital, cyclic, or idiopathic
neutropenia.
Starting Dose:
a) Congenital Neutropenia: The recommended daily starting dose is 6 µg/kg
bid subcutaneously every day.
b) Idiopathic or Cyclic Neutropenia: The recommended daily starting dose is
5 µg/kg as a single injection subcutaneously every day.
Neupogen dose should be reduced if the absolute neutrophil count is
persistently greater than 10,000/ mm 3
Serial CBCs with differential and platelet counts, and an evaluation of
bone marrow morphology and Karyotype should be performed prior to
initiation of Neupogen therapy (see limitations). During the initial 4
weeks of Neupogen therapy and during the 2 weeks following any dose
adjustment, a CBC with differential and platelet count should be performed
twice weekly. Once a patient is clinically stable, a CBC with differential
and platelet count should be performed monthly.
6. Off-label indications: AIDS Leukopenia in children; Amelioration
of leukopenia on AIDS patients on AZT; Amelioration of leukopenia in AIDS
patients with CMV chorioretinitis on Ganciclovir.
Neulasta will be considered reasonable and
necessary for:
1. Cancer Patients Receiving Myelosuppressive regimens
Neulasta is indicated to decrease the incidence of febrile neutropenia and
the duration of neutropenia in patients treated with cytotoxic chemotherapy
for malignancy, with the exception of chronic myeloid leukemia and
myelodysplastic syndromes. American Society for Clinical Oncology
guidelines (ASCO) remain the de facto standard of care unless specifically
superceeded.
Link to ASCO:
2006 Update of Recommendations for the Use of White Blood Cell Growth
Factors: An Evidence-Based Clinical Practice Guideline
Neulasta’s recommended dosage is a single SC injection of 6 mg administered
once per chemotherapy cycle.
Limitations:
Neupogen
· Safety and efficacy of Neupogen has not
been established and are therefore non-covered in: aplastic anemia, hairy
cell leukemia, myelodysplastic disorders, myeloid malignancies (other than
AML), drug induced and congenital agranulocytosis, and alloimmune neonatal
neutropenia.
· Safety and efficacy of Neupogen given in
patients receiving chemotherapy associated with delayed myelosuppression
(e.g., nitrosoureas) or with mitomycin C or with myelosuppressive doses of
anti-metabolites such as 5-fluorouracil has not been established.
· Safety and efficacy of Neupogen in
neonates and patients with autoimmune neutropenia of infancy have not been
established.
· Safety and efficacy of Neupogen in the
treatment of neutropenia due to other hematopoietic disorders as chronic
myeloid leukopenia have not been established.
· Safety and efficacy of Neupogen given
simultaneously with cytotoxic chemotherapy or radiation therapy have not
been established.
· The use of Neupogen prior to confirmation
of Severe Chronic Neutropenia (SCN) may impair diagnostic efforts and
impair or delay evaluation and treatment of an underlying condition other
than SCN and should therefore rule out other diseases associated with
neutropenia prior to administration of Neupogen for SCN.
· Neupogen is
contraindicated in patients with known hypersensitivity to E. coli -derived
proteins, Neupogen, or any component of the product
Neulasta
· Use of Neulasta has not been established
in patients receiving chemotherapy associated with myeloid malignancies,
myelodysplasia, and delayed myelosuppression (e.g. nitrosoureas, mitomycin
C).
· Use of Neulasta has not been established
in patients receiving radiation therapy.
· Administration of Neulasta concomitantly
with 5-fluorouracil or other antimetabolites has not been evaluated in
patients.
· Neulasta should not be administered in
the period between 14 days before and 24 hours after administration of
cytotoxic chemotherapy because of the potential for an increase in
sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy.
· Use of Neulasta is contraindicated in
patients with known hypersensitivity to E. coli derived proteins, Neulasta,
Neupogen, or any other component of the product.
· Safety and effectiveness in pediatric
patients have not been established.
"Least costly alternative” provisions will apply if there develops a
significant disparity between the overall costs of using two medications
which are clinically equivalent for the same indication. Any implementation
of the LCA clause will be triggered by the development of a significant
difference in cost and will be detailed in this policy accompanied by a 45
day notice period.
Neupogen may be covered for other indications or in other circumstances
than those documented in this policy as long as they are not specifically
excluded above. However medical records will have to be provided and must support
the medical necessity in accordance with current outcomes-based standards
of care.
Reasons for Denial
1. Drug given for other than those specified indications listed in this
policy; or used for condition(s) that are contraindicated or investigational;
or the dosage and frequency given is outside the guidelines described.
2. Lack of clinical indication/medical necessity documentation.
3. Documents do not support service billed was rendered.
4. Utilization and billing of inappropriate unit dose that results to an
unreasonable wastage and/or increase dollar amount i.e. using 2 units of
J1440 (300mcg) in lieu of 1 unit of J1441 (480mcg) when dose ordered is
less than 480 mcg but greater than 300 mcg.
Other Comments
1. Normal ANC is considered of 3,000-7,000/mm
2. Neutropenia is defined as a neutrophil count of =500 cells/mm 3,
or a count of <1000 cells/mm 3 with a predicted decrease to
<500 cells/mm 3
3. Severe Chronic Neutropenia is defined as a ANC of < 500/mm.
4. Fever is defined as a single oral temperature of =38.3°C (101°F) or a
temperature of =38.0°C (100.4°F) for =1 h.
5. Febrile Neutropenia is generally designated as a temperature of
approximately 38.5 C (~ 101F) or greater, sustained for more than one hour,
and developing concurrently with an ANC < 500/mm.
6. Medicare will cover the amount of the drug that is reasonable and
necessary for the patient's condition. If a physician must discard the
remainder of a vial after administering a portion to a Medicare patient,
the Medicare program may cover a small, but reasonable amount of discarded
drug, along with the amount administered. Medicare expects this wastage to
be minimal. The provider should make an effort to schedule patients in such
a way that they can minimize any waste and use the drug most efficiently.
Any amount wasted must be clearly documented in the chart with the time,
amount of medication wasted, and the reason for the wastage.
|