Allergic-type reactions occurring on initial or subsequent treatment have been
reported. These have generally been characterized by systemic symptoms involving,
most often skin (rash, urticaria, facial edema), respiratory (wheezing, dyspnea),
and cardiovascular (hypotension, tachycardia) system.
Rapid resolution of symptoms occurred in most cases after administration of antihistamines,
steroids, bronchodilators, and/or epinephrine. Symptoms recurred in more than
half the patients who were rechallenged.
Left upper abdominal pain or shoulder tip pain accompanied by rapid increase
in spleen size should be carefully monitored due to the rare but serious risk
of splenic rupture.
PRECAUTIONS
General Simultaneous Use with
Chemotherapy and Radiation Therapy
The safety and
efficacy of Recombinant G-CSF given simultaneously
with cytotoxic chemotherapy have not been established.
Because of the potential sensitivity of rapidly dividing
myeloid cells to cytotoxic chemotherapy, do not use
Recombinant G-CSF in the period 24 hours before through
24 hours after the administration of cytotoxic chemotherapy.
The safety and efficacy of Recombinant G-CSF have
not been evaluated in-patients receiving concurrent
radiation therapy. Simultaneous use of Recombinant
G-CSF with chemotherapy and radiation therapy should
be avoided.
The safety of Recombinant G-CSF in chronic myeloid leukemia (CML) and myelodysplasia
has not been established.
Leukocytosis
White blood cell
counts of 100,000/mm3 or greater are observed in approximately
2% of patients receiving Recombinant G-CSF at doses
above 5 mcg/kg/day. There were no reports of adverse
events associated with this degree of leukocytosis.
In order to avoid the potential complications of excessive
leukocytosis, a CBC is recommended twice per week during
Recombinant G-CSF.
Cancer Patients Receiving Myelosuppressive
Chemotherapy
A transient increase
in neutrophil counts is typically seen 1 to 2 days
after initiation of Recombinant G-CSF therapy. However,
for a sustained therapeutic response, Recombinant G-CSF
therapy should be continued following chemotherapy
until the post nadir ANC reaches 10,000/mm3.
Increases are observed in serum uric acid, lactate dehydrogenase, and serum alkaline
phosphatase.
Drug Interaction
Drug interactions
between Recombinant G-CSF and other drugs have not
been fully evaluated. Drugs which may potentiate the
release of neutrophils, such as lithium, should be
used with caution.
Carcinogenesis, Mutagenesis,
Impairment of Fertility
The carcinogenic
potential of Recombinant G-CSF has not been studied.
Recombinant G-CSF failed to induce bacterial gene
mutations in either the presence or absence of a
drug metabolizing enzyme system. Recombinant G-CSF
had no observed effect on the fertility of male or
female rats, or on gestation at doses up to 500 mcg/kg.
Pregnancy Category C
Recombinant G-CSF
has been shown to have adverse effects in pregnant
rabbits when given in doses 2 to 10 times the human
dose. Since there are no adequate and well-controlled
studies in pregnant women, the effect, if any, of Recombinant
G-CSF on the developing fetus or the reproductive capacity
of the mother is unknown. However, the scientific literature
describes transplacental passage of Recombinant G-CSF
when administered to pregnant rats during the latter
part of gestation and apparent transplacental passage
of Recombinant G-CSF when administered to pregnant
females by < 30 hours prior to preterm delivery
(< 30 weeks gestation). Recombinant G-CSF should
be used during pregnancy only if the potential benefit
justifies the potential risk to the fetus.
Nursing Mothers
It is not known
whether Recombinant G-CSF is excreted in human milk.
Because many drugs are excreted in human milk, caution
should be exercised if Recombinant G-CSF is administered
to a nursing woman.
Geriatric Use
No overall differences
in safety or effectiveness are observed between elderly
and younger subjects.
ADVERSE REACTIONS
In clinical trials patients
receiving Recombinant G-CSF following nonmyeloablative
cytotoxic chemotherapy, most adverse experiences are the
sequelae of the underlying malignancy or cytotoxic chemotherapy.
Medullary bone pain is the only consistently observed adverse
reaction attributed to Recombinant G-CSF therapy. This
bone pain is generally reported to be of mild-to-moderate
severity, and can be controlled in most patients with non-narcotic
analgesics.
Spontaneously reversible elevations in uric acid, lactate dehydrogenase, and
alkaline phosphatase is seen in patients receiving Recombinant G-CSF therapy
following cytotoxic chemotherapy; increases were generally mild-to-moderate.
There are no serious, life-threatening, or fatal adverse reactions attributed
to Recombinant G-CSF therapy.
OVERDOSAGE
In cancer patients receiving Recombinant G-CSF as an adjunct to myelosuppressive
chemotherapy, it is recommended, to avoid the potential risks of excessive leukocytosis
that Recombinant G-CSF therapy be discontinued if the ANC surpasses 10,000/mm3
after the chemotherapy-induced ANC nadir has occurred.
Patients in the BMT studies received up to 138 mcg/kg/day without toxic effects,
although there was a flattening of the dose response curve above daily doses
of greater than 10 mcg/kg/day.
DOSAGE AND ADMINISTRATION
Cancer Patients Receiving Myelosuppressive
Chemotherapy
The recommended
starting dose of Recombinant G-CSF is 5 mcg/kg/day,
administered as a single daily injection by SC bolus
injection, by short IV infusion (15 to 30 minutes),
or by continuous SC or continuous IV infusion. A
CBC and platelet count should be obtained before
instituting Recombinant G-CSF therapy, and monitored
twice weekly during therapy. Doses may be increased
in increments of 5 mcg/kg for each chemotherapy cycle,
according to the duration and severity of the ANC
nadir.
Recombinant G-CSF should be administered no earlier than 24 hours after the administration
of cytotoxic chemotherapy. Recombinant G-CSF should not be administered in the
period 24 hours before the administration of chemotherapy.
Cancer Patients Receiving Bone
Marrow Transplant
The recommended
dose of Recombinant G-CSF following BMT is 10 mcg/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 Recombinant G-CSF should be administered
at least 24 hours after cytotoxic chemotherapy and
at least 24 hours after bone marrow infusion.
Peripheral Blood Progenitor
Cell Collection and Therapy in Cancer Patients
The recommended dose of Recombinant G-CSF for the mobilization of PBPC is 10
mcg/kg/day SC, either as a bolus or a continuous infusion. It is recommended
that Recombinant G-CSF be given for at least 4 days before the first leukapheresis
procedure and continued until the last leukapheresis.
Dilution
If required, Recombinant G-CSF may be diluted in 5% dextrose. Recombinant G-CSF
diluted to concentrations between 5 and 15 mcg/mL should be protected from
adsorption to plastic materials by the addition of Albumin (Human) to a final
concentration of 2 mg/mL. When diluted in 5% dextrose or 5% dextrose plus Albumin
(Human), Recombinant G-CSF is compatible with glass bottles, PVC and polyolefin
IV bags, and polypropylene syringes.
Dilution of Recombinant G-CSF to a final concentration of less than 5 mcg/mL
is not recommended at any time.
Do not dilute with saline at any time; product may precipitate.
Storage
Neukine should
be stored in the refrigerator at 2° to 8°C
(36° to 46°F). Avoid shaking. Prior to injection,
Neukine may be allowed to reach room temperature
for a maximum of 24 hours. Any vial or prefilled
syringe left at room temperature for greater than
24 hours should be discarded.
HOW SUPPLIED
Single-dose, prefilled
syringe of 1 ml containing 300 mcg of rHu G-CSF.
